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1.
JAMA ; 323(15): 1456-1466, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32315057

RESUMO

Importance: A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. Objective: To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. Design, Setting, and Participants: A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Interventions: Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. Main Outcomes and Measures: The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Results: Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. Trial Registration: anzctr.org.au Identifier: ACTRN12613000039785.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças da Medula Óssea/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Medula Óssea/patologia , Doenças da Medula Óssea/complicações , Doenças da Medula Óssea/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/patologia , Falha de Tratamento , Ácido Zoledrônico/administração & dosagem
2.
Ann Rheum Dis ; 79(4): 525-528, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32098758

RESUMO

OBJECTIVES: In the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location. METHODS: Patients were randomised 1:1:1:1:1 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects. RESULTS: Thinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference: 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference: 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects. CONCLUSIONS: Sprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results. TRIAL REGISTRATION NUMBER: NCT01919164.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Fatores de Crescimento de Fibroblastos/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cartilagem Articular/patologia , Método Duplo-Cego , Feminino , Humanos , Injeções Intra-Articulares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia
3.
Medicine (Baltimore) ; 99(8): e18912, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080074

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of degenerative arthritis. We used Phellinus linteus (PL), which has been well-known anti-inflammatory function. In this study, we will evaluate if PL extract improves symptoms with KOA. METHODS: This study will be an 8-week single-center randomized controlled double-blind clinical trial. Total of 24 subjects with KOA will be enrolled and they will be divided into 3 groups, PL 1,000 mg, PL 1,500 mg and placebo. Subjects will be followed up every 4 weeks with efficacy and safety at the 2nd and 3rd visits. All subjects should maintain a dosage schedule for this protocol. The primary outcome will be assessed with the Korean version of the Western Ontario and McMasters Universities. And the secondary outcomes will be measured using the visual analog scale, quality of life scale (EQ-5D-3L), ESR, C-reactive protein, and C-telopeptide of type-II collagen. Statistical analysis will be performed on the principle of full analysis set. DISCUSSION: This study has inclusion and exclusion criteria and a well-controlled intervention. This clinical trial is the first step to assess the efficacy and safety of PL in patients with KOA. This study will make an important contribution to the literature and aid follow-up research into the use of PL in KOA.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Administração Oral , Adulto , Idoso , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/efeitos dos fármacos , Colágeno Tipo I/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/patologia , Peptídeos/efeitos dos fármacos , Placebos/administração & dosagem , Extratos Vegetais/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , República da Coreia/epidemiologia , Resultado do Tratamento
4.
Am J Clin Nutr ; 111(3): 667-676, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31912140

RESUMO

BACKGROUND: While some individual foods and nutrients have been associated with knee osteoarthritis (KOA) progression, the association between dietary patterns and KOA progression has received little research attention. OBJECTIVE: The objective of this study was to determine whether dietary patterns, derived by principal components analysis (PCA), are associated with KOA progression. METHODS: In the Osteoarthritis Initiative (OAI), a prospective cohort with clinical centers in Maryland, Ohio, Pennsylvania, and Rhode Island, 2757 participants with existing KOA (mean age 62 y) and diet assessed at baseline were followed for ≤72 mo. Using PCA, Western and prudent dietary patterns were derived. Radiographic KOA progression was assessed using 2 separate measures, 1 full Kellgren-Lawrence (KL) grade increase and loss in joint space width (JSW). Symptomatic KOA progression was defined as an increase in or remaining in 1 of the 2 highest classification categories of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). RESULTS: Adherence to Western and prudent dietary patterns was significantly associated with radiographic and symptomatic progression of KOA. With increasing Western pattern score, there was increased KL-worsening risk (compared with quartile 1, HR for quartile 4: 1.30; 95% CI: 1.05, 1.61; P-trend < 0.01) and increased odds of progression to higher WOMAC score (compared with quartile 1, OR for quartile 4: 1.39; 95% CI: 1.18, 1.63; P-trend < 0.01) but no significant change in JSW loss. With increasing prudent pattern score there was decreased KL-worsening risk (compared with quartile 1, HR for quartile 4: 0.79; 95% CI: 0.64, 0.98; P-trend = 0.02), decreased JSW loss (quartile 1: 0.46 mm; quartile 4: 0.38 mm; P-trend < 0.01), and decreased odds of higher WOMAC progression (compared with quartile 1, OR for quartile 4 0.73; 95% CI: 0.62, 0.86; P-trend < 0.01) in multivariable adjusted models. CONCLUSIONS: Adherence to a Western dietary pattern was associated with increased radiographic and symptomatic KOA progression, while following a prudent pattern was associated with reduced progression. In general, for people already diagnosed with KOA, eating a diet rich in fruits, vegetables, fish, whole grains, and legumes may be related to decreased radiographic and symptomatic disease progression.


Assuntos
Dieta Ocidental/efeitos adversos , Osteoartrite do Joelho/metabolismo , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Estudos Prospectivos , Índice de Gravidade de Doença
5.
PLoS One ; 15(1): e0226501, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978052

RESUMO

Transparent research in musculoskeletal imaging is fundamental to reliably investigate diseases such as knee osteoarthritis (OA), a chronic disease impairing femoral knee cartilage. To study cartilage degeneration, researchers have developed algorithms to segment femoral knee cartilage from magnetic resonance (MR) images and to measure cartilage morphology and relaxometry. The majority of these algorithms are not publicly available or require advanced programming skills to be compiled and run. However, to accelerate discoveries and findings, it is crucial to have open and reproducible workflows. We present pyKNEEr, a framework for open and reproducible research on femoral knee cartilage from MR images. pyKNEEr is written in python, uses Jupyter notebook as a user interface, and is available on GitHub with a GNU GPLv3 license. It is composed of three modules: 1) image preprocessing to standardize spatial and intensity characteristics; 2) femoral knee cartilage segmentation for intersubject, multimodal, and longitudinal acquisitions; and 3) analysis of cartilage morphology and relaxometry. Each module contains one or more Jupyter notebooks with narrative, code, visualizations, and dependencies to reproduce computational environments. pyKNEEr facilitates transparent image-based research of femoral knee cartilage because of its ease of installation and use, and its versatility for publication and sharing among researchers. Finally, due to its modular structure, pyKNEEr favors code extension and algorithm comparison. We tested our reproducible workflows with experiments that also constitute an example of transparent research with pyKNEEr, and we compared pyKNEEr performances to existing algorithms in literature review visualizations. We provide links to executed notebooks and executable environments for immediate reproducibility of our findings.


Assuntos
Algoritmos , Cartilagem Articular/patologia , Fêmur/patologia , Interpretação de Imagem Assistida por Computador/métodos , Articulação do Joelho/patologia , Imagem por Ressonância Magnética/métodos , Osteoartrite do Joelho/patologia , Humanos , Reprodutibilidade dos Testes , Fluxo de Trabalho
6.
Bone Joint J ; 102-B(1): 132-136, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31888367

RESUMO

AIMS: We report the natural course of Baker's cysts following total knee arthroplasty (TKA) at short- and mid-term follow-up. METHODS: In this prospective case series, 105 TKA patients were included. All patients who received surgery had a diagnosis of primary osteoarthritis and had preoperatively presented with a Baker's cyst. Sonography and MRI were performed to evaluate the existence and the gross size of the cyst before TKA, and sonography was repeated at a mean follow-up time of 1.0 years (0.8 to 1.3; short-term) and 4.9 years (4.0 to 5.6; mid-term) after TKA. Symptoms potentially attributable to the Baker's cyst were recorded at each assessment. RESULTS: At the one-year follow-up analysis, 102 patients were available. Of those, 91 patients were available for the 4.9-year assessment (with an 86.7% follow-up rate (91/105)). At the short- and mid-term follow-up, a Baker's cyst was still present in 87 (85.3%) and 30 (33.0%) patients, respectively. Of those patients who retained a Baker's cyst at the short-term follow-up, 31 patients (35.6%) had popliteal symptoms. Of those patients who continued to have a Baker's cyst at the mid-term follow-up, 17 patients (56.7%) were still symptomatic. The mean preoperative cyst size was 14.5 cm2 (13.1 to 15.8). At the short- and mid-term follow-up, the mean cyst size was 9.7 cm2 (8.3 to 11.0) and 10.4 cm2 (9.8 to 11.4), respectively. A significant association was found between the size of the cyst at peroperatively and the probability of resolution, with lesions smaller than the median having an 83.7% (36/43) probability of resolution, and larger lesions having a 52.1% (25/48) probability of resolution (p < 0.001). At the mid-term follow-up, no association between cyst size and popliteal symptoms was found. CONCLUSION: At a mean follow-up of 4.9 years (4.0 to 5.6) after TKA, the majority (67.0%, 61/91) of the Baker's cysts that were present preoperatively had disappeared. The probability of cyst resolution was dependent on the size of the Baker's cyst at baseline, with an 83.7% (36/43) probability of resolution for smaller cysts and 52.1% (25/48) probability for larger cysts. Cite this article: Bone Joint J. 2020;102-B(1):132-136.


Assuntos
Artroplastia do Joelho/métodos , Cisto Popliteal/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Cisto Popliteal/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia
7.
J Ethnopharmacol ; 248: 112277, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31606533

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Knee osteoarthritis (OA) cause pain and edema, as well as unbalance between the production of reactive oxygen species and antioxidant activity. These problems interfere with the articular function, leading to a significant loss of life quality. Sida tuberculata R.E.Fr. is an herbaceous plant belonging to the Malvaceae family found in southern Brazil. This plant has traditionally been consumed as an aqueous extract and popularly used in the treatment of many diseases, with antioxidant and antimicrobial activity, reducing pain and inflammation. AIM OF THE STUDY: To verify the effects of S. tuberculata extract obtained from leaves on oxidative, toxic and nociceptive parameters induced by knee OA in rats. MATERIALS AND METHODS: Aqueous extracts of S. tuberculata were evaluated under phytochemical analyses. Knee Osteoarthritis was induced in rats with monosodium iodoacetate (1.5 mg/50 µl) and treated with S. tuberculata extract. The animals were treated orally with 3 doses of S. tuberculata extract (STE): 1.5, 5 and 15 mg/ml, for 14 days. For biochemical analyses, the following tests were performed: lipid peroxidation, carbonylated protein content, superoxide dismutase activity, non-protein thiol levels and myeloperoxidase activity. For the evaluation of pain and edema we verify mechanical and thermal hyperalgesia, spontaneous pain observation and measurement of knee edema with a caliper. For histological evaluations, the animal knee joints were removed. For toxicity evaluation, the levels of aspartate aminotransferase, alanine aminotransferase and urea, as well as the relative weight of the organs were analyzed. RESULTS: The S. tuberculata phytochemical analyses showed the majority peak corresponding to 20-hydroxyecdysone (20HE). The plant extract decreased damages related to oxidative stress in the blood serum (lipid peroxidation and carbonyl content) Overall, the STE 5 mg Group presented the greater statistical significance, in the blood serum samples, in relation to the other groups, being the most relevant result. The S. tuberculata groups presented pain decrease, lower neutrophil activity in the knee, and increased blood serum activity. The animals of S. tuberculata groups showed a decrease in mechanical hyperalgesia. The animals treated also presented lower scores for spontaneous pain. It was observed that the dose of 5 mg presented, once again, more expressive results, since the animals of this group had a higher frequency (greater number of days) with significant decrease of pain. In the histological analysis, in the STE 5 mg group, the articular cartilage lesions were observed at an intermediate point between the damage found in the MIA and Diclofenac groups. Besides that, the STE did not show significant changes in oxidative stress damage in liver and kidney samples. Blood serum samples did not indicate significant differences in liver and renal function. As well as, there were no differences in mean relative body weights in relation to control groups (Salina and MIA). CONCLUSION: S. tuberculata reduced the damage due to oxidative stress and pain caused by knee osteoarthritis in rats. In addition, the extract presented no toxicity. Our results suggest that S. tuberculata seems to have a therapeutic potential in the osteoarthritis treatment.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Malvaceae , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Estresse Oxidativo/efeitos dos fármacos , Dor/metabolismo , Peroxidase/metabolismo , Extratos Vegetais/farmacologia , Ratos Wistar , Superóxido Dismutase/metabolismo
8.
Eur Radiol ; 30(1): 128-140, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31297634

RESUMO

OBJECTIVES: Given the coexistence and possible interactions between patellofemoral and tibiofemoral compartments, roles of patellofemoral morphology measurements in tibiofemoral osteoarthritis (OA) have not been investigated extensively. We aimed to determine whether patellofemoral morphology is associated with the presence and longitudinal worsening of tibiofemoral OA in participants of the Osteoarthritis Initiative (OAI). METHODS: Baseline knee MRIs of 600 participants were read by two independent blinded observers in consensus to determine patellofemoral morphology measurements including tibial tuberosity to trochlear groove (TT-TG) distance, trochlear groove depth (TGD), lateral patellar tilt (LPT), and Insall-Salvati ratio (ISR). Radiographic and MRI OA knee scoring (MOAKS) measurements were extracted from baseline and 2-year follow-up readings. Associations between baseline patellofemoral morphology metrics with radiographic medial tibiofemoral compartment (MTFC) joint space loss (> 0.7 mm, between baseline and 2nd-4th-year readings), and MRI-derived cartilage damage, bone marrow lesions (BMLs), and osteophytes (baseline to 2 years), were investigated using regression models adjusted for age, sex, body mass index, and knee alignment. P values were corrected using the Benjamini-Hochberg procedure. RESULTS: Patellofemoral morphology measurements were not associated with longitudinal joint space loss in the MTFC or MOAKS determinants. Only TT-TG distance was associated with the baseline number of subregions with cartilage defects (OR (95% CI), 1.09 (1.04-1.14), corrected p value ≤ 0.01), BMLs (OR (95% CI), 1.1 (1.04-1.17), corrected p value = 0.01), and osteophytes (OR (95% CI), 1.09 (1.05-1.14), corrected p value ≤ 0.01) in the lateral tibiofemoral compartment (LTFC), and worsening of LTFC cartilage defects over 2 years (OR (95% CI), 1.09 (1.03-1.16), corrected p value = 0.02). CONCLUSIONS: Higher TT-TG distance was associated with concurrent MRI-derived OA-related structural damages and 2-year follow-up worsening only in LTFC. No associations were detected between patellofemoral morphology measurements and MTFC OA progression. KEY POINTS: • Of all patellofemoral morphology measurements, the only lateralization of the tibial tubercle may be considered as a risk factor for lateral (not medial) tibiofemoral osteoarthritis worsening. • Patellofemoral morphology measurements of patella alta, trochlear dysplasia, patellar tilt, and lateralization of the tibial tubercle are not associated with radiographic and MRI-based medial tibiofemoral osteoarthritis worsening over 2 years. • Using longitudinal MRI data, each millimeter increase of TT-TG distance is associated with a 9% (95% confidence interval, 3-16%) increase in odds of longitudinal cartilage defects in the lateral tibiofemoral (but not medial) compartment over 2 years.


Assuntos
Osteoartrite do Joelho/patologia , Articulação Patelofemoral/patologia , Adulto , Medula Óssea/patologia , Doenças das Cartilagens/patologia , Feminino , Humanos , Articulação do Joelho/patologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Osteófito/patologia , Patela/patologia , Radiografia/métodos , Tíbia/patologia
9.
J Ethnopharmacol ; 247: 112261, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31577939

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Loganin is a major iridoid glycoside and one of the quality control indexes of CF. In TCM clinical practice, prescription containing CF is commonly used to treat osteoarthritis (OA), but the underlying mechanisms of loganin are not yet utterly understood. AIM OF THE STUDY: The aims of the present study are to confirm the therapeutic effects of loganin in an OA mouse model and to determine the mechanisms involved in the OA protective effects. MATERIALS AND METHODS: The destabilization of the medial meniscus (DMM) procedure was performed on the right knee of 8-week-old C57BL/6 male mice. 30 or 100 µg/ml of loganin was then injected into articular space twice a week for 8 and 12-week. Safranin O/Fast green staining, H&E staining, micro-CT analysis were performed to analyze structural and morphological changes. The protein expression of collagen type II (Col2), metalloproteinase-3 (Mmp3), matrix metalloproteinase 13 (Mmp13) collagen type X (Col10), cryopyrin and caspase-1 were detected by immunochemistry staining. Immuno-fluorescence assay was performed to assess changes in expression of CD31, endomucin, p65 and p-I-κB. RESULTS: Results of histomorphometry showed that loganin delays the progression of OA in the DMM model. In cartilage, loganin decreased the OARSI score, increasing hyaline cartilage (HC) thickness and decreasing calcified cartilage (CC) thickness. Moreover, loganin inhibited osteophyte formation, reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th) and increased trabecular separation (Tb.Sp) in subchondral bone. Mechanistically, loganin increased the expressions of Col2, decreases the expression of Mmp3, Mmp13, Col10, cryopyrin and caspase-1 in cartilage. In parallel, loganin inhibited the expression of CD31 and endomucin in subchondral bone. Furthermore, loganin suppressed nuclear translocation of p65 protein, and decreased the amount of p-I-κB in chondrocytes. CONCLUSIONS: In summary, these results uncovered that loganin inhibits NF-κB signaling and attenuates cartilage matrix catabolism and pyroptosis of chondrocytes in articular cartilage. Loganin may serve as a potential therapeutic agent for OA treatment.


Assuntos
Cornus/química , Iridoides/farmacologia , Meniscos Tibiais/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Animais , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Colágeno Tipo II/metabolismo , Colágeno Tipo X/metabolismo , Modelos Animais de Doenças , Frutas/química , Humanos , Iridoides/isolamento & purificação , Iridoides/uso terapêutico , Masculino , Meniscos Tibiais/citologia , Meniscos Tibiais/patologia , Meniscos Tibiais/cirurgia , Camundongos , NF-kappa B/imunologia , NF-kappa B/metabolismo , Osteoartrite do Joelho/imunologia , Osteoartrite do Joelho/patologia , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
10.
Med Sci Monit ; 25: 10057-10066, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881548

RESUMO

BACKGROUND Magnetic resonance imaging (MRI) of osteoarthritis (OA) of the knee is a preoperative method of joint assessment. Histology of the joint is invasive and performed after surgery. T1rho/T2 MRI mapping is a new preoperative method of quantifying joint changes. This study aimed to analyze and compare the histological changes in the joint cartilage with the use of quantitative T1rho/T2 MRI mapping in patients with OA of the knee. MATERIAL AND METHODS Twenty patients with OA of the knee (20 knees) underwent preoperative MRI with T1rho mapping, T2 mapping, T1-weighted, and T2-weighted fat-suppressed MRI sequences. The degree of OA of the knee on MRI was graded according to the Osteoarthritis Research Society International (OARSI) criteria and the Kellgren-Lawrence grading system. Histological grading of OA used the OARSI criteria. Four tibiofemoral condyles were assessed histologically, and the degree of cartilage destruction was determined using the OARSI criteria. Two investigators performed cartilage segmentation for T1rho/T2 values. RESULTS Histology of the four knee joint condyles confirmed mild to severe OA. The histology of the cartilage thickness (P<0.001) and the MRI findings of the distal medial condyle (P<0.00) were significantly different from the other three knee joint condyles. The T2 and T1rho values of each condyle were significantly correlated with the histological grade (II-IV) of the joint condyles, including the cartilage volume, cartilage defects, thickness, and bone lesions (P<0.05). CONCLUSIONS In 20 patients with OA of the knee, preoperative T2/T1rho MRI identified Grade II-IV OA changes in the joint.


Assuntos
Imagem por Ressonância Magnética , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Idoso , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Cartilagem/diagnóstico por imagem , Cartilagem/patologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Osteófito , Tíbia/patologia , Tíbia/cirurgia , Escala Visual Analógica
11.
PLoS One ; 14(12): e0226986, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860662

RESUMO

PURPOSE: To demonstrate the production of inflammatory mediators by cells located in bone marrow spaces inside rodent menisci. METHODS: Mice subjected to transection of the medial collateral and anterior cruciate ligaments and meniscotomy (osteoarthritis model) or to a sham procedure, as well as non-operated (naive) mice and rats, had knee joints excised. Tissues were stained with hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP). CD68+ cells, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, and tumor necrosis factor (TNF) expression were detected using immunohistochemistry. RESULTS: Lamellar ossified areas, bone-entrapped osteocytes and bone marrow spaces were found inside menisci of one week up to 6 months-old naïve mice, regardless of gender. Menisci from naive rats also showed the same pattern with bone marrow areas. CD68+ cells were identified in bone marrow areas inside the meniscus of mice. TRAP+ osteoclasts, and hematogenous precursors expressing IL-1ß, TNF, and iNOS were identified inside bone marrow areas in meniscal samples from both naïve and sham operated mice. Quantitative immunoexpression of IL-1 ß, TNF and iNOS was more intense, P = 0.0194, 0.0293, 0.0124, respectively, in mouse knees from mice sacrificed 49 days after being subjected to an osteoarthritis (OA) model as compared to sham operated animals. CONCLUSION: We provide novel data showing that rodent menisci display bone marrow areas with cells able to produce inflammatory mediators. Immunoexpression of inflammatory mediators in those bone marrow areas is significantly more pronounced in mice subjected to experimental OA.


Assuntos
Medula Óssea/patologia , Mediadores da Inflamação/metabolismo , Menisco/patologia , Osteoartrite do Joelho/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Modelos Animais de Doenças , Feminino , Interleucina-1beta/metabolismo , Articulação do Joelho/cirurgia , Masculino , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite do Joelho/patologia , Osteoclastos/metabolismo , Ratos , Ratos Wistar , Fosfatase Ácida Resistente a Tartarato/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Org Biomol Chem ; 17(46): 9913-9923, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31720670

RESUMO

Nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) inhibitors have been suggested as a potential treatment for calcium pyrophosphate dihydrate (CPPD) deposition disease. Here, we targeted the development of improved NPP1 inhibitors based on acyclic mimics of Pα,α-phosphorodithioate-substituted adenine nucleotides, 7-10. The latter were obtained in a facile two-step synthesis from adenine-(methoxy)ethanol. Among analogs 7-10, adenine-(methoxy)ethoxy-Pα,α-dithio-triphosphate, 8, was the most potent NPP1 inhibitor both with purified enzyme (IC50 0.645 µM) and in osteoarthritic human chondrocytes (IC50 0.033 µM). Furthermore, it efficaciously (10-fold vs. control) inhibited ATP-induced CPPD in human articular chondrocytes. Importantly, 8 was a highly selective NPP1 inhibitor which showed only minor inhibition of NPP3, CD39 and CD73, and did not inhibit TNAP (tissue nonspecific alkaline phosphatase) activity in human chondrocytes. Furthermore, 8 did not activate P2Y1,2,6 receptors. Analog 8 was not toxic to cultured chondrocytes at 100 µM. Therefore, 8 may be suitable for further development as a drug candidate for the treatment of CPPD arthritis and other NPP1-related diseases.


Assuntos
Adenina/farmacologia , Pirofosfato de Cálcio/antagonistas & inibidores , Condrócitos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Polifosfatos/farmacologia , Pirofosfatases/antagonistas & inibidores , Compostos de Sulfidrila/farmacologia , Adenina/síntese química , Adenina/química , Pirofosfato de Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Diester Fosfórico Hidrolases/metabolismo , Polifosfatos/química , Pirofosfatases/metabolismo , Relação Estrutura-Atividade , Compostos de Sulfidrila/química
13.
Expert Opin Drug Metab Toxicol ; 15(12): 1021-1032, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31709838

RESUMO

Introduction: Osteoarthritis (OA) is the leading cause of disability in the elderly, usually presenting with mono-or oligo-arthritis where local drug delivery by intra-articular (IA) injection may be more effective in terms of increased bioavailability, less systemic exposure and reduced adverse events. Several intra-articular medications for symptomatic are available on the market while the new disease-modifying drugs (DMOADs) are progressing into phase 3 pipeline of drug development.Areas covered: This narrative review covered the pharmacokinetic and pharmacodynamics of clinically available IA drugs which include corticosteroids, hyaluronic acid as well as injection techniques, efficacy, adverse effects and contraindications. In addition, the authors briefly describe the newer disease-modifying OA drugs (DMOAD) which are undergoing phase 3 pipeline of development such as Fibroblast growth factor (FGF-18) and Wnt inhibitor.Expert opinion: This is a rapidly evolving area with both new products and new trials regularly emerging. It is also a critically important area in a disease field that lacks for safe and effective treatments, where intra-articular delivery may enhance both local efficacy and reduce systemic toxicity.


Assuntos
Antirreumáticos/administração & dosagem , Desenvolvimento de Medicamentos , Osteoartrite do Joelho/tratamento farmacológico , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Glucocorticoides/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intra-Articulares , Osteoartrite do Joelho/patologia
14.
JAMA ; 322(14): 1360-1370, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593273

RESUMO

Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug. Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis. Design, Setting, and Participants: FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported. Interventions: Participants were randomized to 1 of 5 groups: intra-articular injections of 100 µg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 µg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks. Main Outcomes and Measures: The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%). Results: Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 µg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 µg of sprifermin every 12 months; 0.02 mm (95% CI, -0.01 to 0.04 mm) for 30 µg of sprifermin every 6 months; and 0.01 mm (95% CI, -0.01 to 0.03 mm) for 30 µg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 µg of sprifermin administered every 6 months or every 12 months, or for 30 µg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 µg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 µg of sprifermin every 12 months: n = 50 [45.0%]; 30 µg of sprifermin every 6 months: n = 40 [36.0%]; and 30 µg of sprifermin every 12 months: n = 48 [44.0%]). Conclusions and Relevance: Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 µg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 µg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain. Trial Registration: ClinicalTrials.gov Identifier: NCT01919164.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cartilagem Articular/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Fatores de Crescimento de Fibroblastos/efeitos adversos , Seguimentos , Humanos , Injeções Intra-Articulares , Articulação do Joelho , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia
15.
Int J Mol Sci ; 20(19)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569601

RESUMO

BACKGROUND: The goal of this study was to determine if adenovirus-delivered LOXL2 protects against progressive knee osteoarthritis (OA), assess its specific mechanism of action; and determine if the overexpression of LOXL2 in transgenic mice can protect against the development of OA-related cartilage damage and joint disability. METHODS: Four-month-old Cho/+ male and female mice were intraperitoneally injected with either Adv-RFP-LOXL2 or an empty vector twice a month for four months. The proteoglycan levels and the expression of anabolic and catabolic genes were examined by immunostaining and qRT-PCR. The effect of LOXL2 expression on signaling was tested via the pro-inflammatory cytokine IL1ß in the cartilage cell line ATDC5. Finally; the OA by monosodium iodoacetate (MIA) injection was also induced in transgenic mice with systemic overexpression of LOXL2 and examined gene expression and joint function by treadmill tests and assessment of allodynia. RESULTS: The adenovirus treatment upregulated LOXL2; Sox9; Acan and Runx2 expression in both males and females. The Adv-RFP-LOXL2 injection; but not the empty vector injection increased proteoglycan staining and aggrecan expression but reduced MMP13 expression. LOXL2 attenuated IL-1ß-induced phospho-NF-κB/p65 and rescued chondrogenic lineage-related genes in ATDC5 cells; demonstrating one potential protective mechanism. LOXL2 attenuated phospho-NF-κB independent of its enzymatic activity. Finally; LOXL2-overexpressing transgenic mice were protected from MIA-induced OA-related functional changes; including the time and distance traveled on the treadmill and allodynia. CONCLUSION: Our study demonstrates that systemic LOXL2 adenovirus or LOXL2 genetic overexpression in mice can protect against OA. These findings demonstrate the potential for LOXL2 gene therapy for knee-OA clinical treatment in the future.


Assuntos
Envelhecimento/genética , Aminoácido Oxirredutases/genética , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Adenoviridae/genética , Aminoácido Oxirredutases/metabolismo , Animais , Artrite Experimental , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Modelos Animais de Doenças , Progressão da Doença , Expressão Gênica , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Interleucina-1beta/metabolismo , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Osteoartrite do Joelho/metabolismo , Transdução Genética
16.
Pain Res Manag ; 2019: 7684762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662813

RESUMO

Background: The aim of this study was to analyse the relationship between the clinical manifestations, disease severity based on radiography images, functional activity level, and quality of life in patients with knee osteoarthritis in a rural population living in Serbian enclaves in Kosovo, as well as to determine the correlation between the WOMAC and the EQ-5D questionnaire in this population. Method: The cross-sectional study was conducted at the Internal Medicine Clinic, Clinical Hospital Center Pristina-Gracanica, located in Laplje Selo from February to December 2013. One hundred patients with confirmed (American College of Rheumatology criteria) knee osteoarthritis completed the EQ-5D and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires, rated pain on a visual analogue scale (VAS), and underwent knee radiographic examinations. Result: Most patients were obese with moderate radiographic changes according to the Kellgeren-Lawrence scale and suffered from very severe pain according to the VAS scale. The duration of disease significantly correlated with the WOMAC scores, VAS score, and all of the scores on the EQ-5D, except for mobility. The age of participants showed a similar correlation with the same variables. The patients with higher Kellgren-Lawrence scores (3-4) were significantly older, with a significantly higher body mass index (BMI) and longer duration of disease than patients with lower scores (1-2). Significantly higher VAS, pain/discomfort EQ-5D, and WOMAC pain and function scores were also recorded among patients with more significant radiological changes. The correlations between WOMAC and EQ-5D were satisfactory. Conclusion: The severity of clinical manifestations and radiographic area changes may affect functional ability and the quality of life in knee OA patients living in rural areas, which requires adequate treatment and physical therapy.


Assuntos
Osteoartrite do Joelho/patologia , Qualidade de Vida , Atividades Cotidianas , Idoso , Estudos Transversais , Fazendeiros , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Dor/etiologia , População Rural , Inquéritos e Questionários
17.
Clin Exp Rheumatol ; 37 Suppl 120(5): 96-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621573

RESUMO

Knee pain in osteoarthritis is complex and complicated by the fact that osteoarthritis is considered to be a disorder of multiple phenotypes. This complexity challenges our understanding as to why some people remain relatively symptom-free, while others progress to persistent pain. One approach to understanding the mechanisms underlying the transition to persistent pain is by identifying pain susceptibility phenotypes in people with or at risk of knee osteoarthritis. Using variables representative of the multidimensional nature of pain in people who were free of persistent pain, we identified four phenotypes characterised by low pressure pain thresholds and temporal summation and not psychosocial factors in those who developed persistent pain two years later. The group with the highest proportion of low pressure pain thresholds and a moderate proportion with facilitated temporal summation had twice the odds of developing persistent knee pain. This work provides preliminary insights into the critical importance of altered neurobiological mechanisms of pain signalling that contributes to development of chronic, persistent pain in knee osteoarthritis.


Assuntos
Dor Crônica , Osteoartrite do Joelho , Medição da Dor , Humanos , Articulação do Joelho , Osteoartrite do Joelho/patologia , Limiar da Dor , Fenótipo
18.
Molecules ; 24(19)2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557835

RESUMO

Pain is recognized as one of the main symptoms in knee osteoarthritis and is the main reason why patients seek medical attention. Scoparia dulcis has been popularly used to relieve discomfort caused by various painful conditions. The objective of the study is to evaluate the analgesic and anti-inflammatory effect of the crude extract of S. dulcis, in an experimental model of osteoarthritis. The experiment was performed with Wistar rats divided into 4 groups with 5 animals each: healthy, saline, crude extract, and meloxicam groups. Knee osteoarthritis was induced by intra-articular injection of sodium mono-iodoacetate. First, clinical parameters of pain were assessed at days 0, 5, 10, 15, and 20 after induction. Second, the potential cyclooxygenase inhibition was evaluated, and the cytokines of the synovial fluid were quantified. An in silico test and Molecular Docking tests were performed. A histopathological evaluation was made on articular cartilage with safranin O staining. The results showed that a 15-day treatment with crude extract reduced edema, spontaneous pain, peripheral nociceptive activity, and proinflammatory cytokines in the synovial fluid. The highest inhibition of cyclooxygenase 2 in the crude extract occurred at 50 µg/mL. The crude extract of S. dulcis presents therapeutic potential for the treatment of osteoarthritis due to its anti-inflammatory and anti-nociceptive action.


Assuntos
Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Extratos Vegetais/farmacologia , Scoparia/química , Animais , Biomarcadores , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Camundongos , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/metabolismo , Extratos Vegetais/química , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Espectrometria de Massas por Ionização por Electrospray
19.
BMC Musculoskelet Disord ; 20(1): 407, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484517

RESUMO

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder among elderly individuals. Nonsurgical treatment plays an important role in treating knee OA. The aim of the present study was to investigate the trends and research status about nonsurgical treatment of knee OA. METHODS: Publications about the nonsurgical treatment of knee OA from 1994 to 2018 were searched from the Web of Science (WoS) database. The data were analyzed by using bibliometric methodology. The software VOSviewer was used for bibliographic coupling, coauthorship, cocitation, co-occurrence analysis and to investigate the publication trends in nonsurgical treatment of knee OA. RESULTS: In total, 8512 articles were included. The number of publications increased annually worldwide. The United States has made the largest contribution to this field, with the most publications, citations and the highest H-index. The most contributive institutions were Harvard University, the University of California system and Assistance Publique Hopitaux Paris (APHP). The journal Osteoarthritis and Cartilage published the most relative articles. Studies could be classified into five clusters: articular cartilage study, biomechanics study, physiotherapy study, oral pharmacologic study and intra-articular injection study. Articular cartilage and physiotherapy were predicted as the next hot topics in this field. CONCLUSIONS: There will be an increasing number of publications on the nonsurgical treatment of knee OA based on current global trends. The United States made the largest contribution to this field. More focus will be placed on cartilage-related and physiotherapy research, which may be the next popular topics in the nonsurgical treatment of knee OA.


Assuntos
Bibliometria , Pesquisa Biomédica/estatística & dados numéricos , Osteoartrite do Joelho/terapia , Administração Oral , Anti-Inflamatórios/administração & dosagem , Fenômenos Biomecânicos , Pesquisa Biomédica/tendências , Cartilagem Articular/patologia , Humanos , Injeções Intra-Articulares/estatística & dados numéricos , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/fisiopatologia , Modalidades de Fisioterapia/estatística & dados numéricos
20.
BMC Musculoskelet Disord ; 20(1): 417, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492126

RESUMO

BACKGROUND: Biomechanical changes in articular cartilage are associated with the onset of osteoarthritis. We developed an optical coherence tomography-based strain rate tomography method: stress relaxation optical coherence straingraphy (SR-OCSA). The purpose of this study was to establish an approach for measuring mechanical properties of articular cartilage using SR-OCSA, and to investigate the distribution of viscoelastic properties of articular cartilage in early osteoarthritis. METHODS: Anterior cruciate ligament transection surgery was performed on the left knees of 8-9-month-old New Zealand white rabbits. SR-OCSA was used to visualize and measure the viscoelastic properties of articular cartilage via attenuation coefficient of strain rate (ACSR). Using the same conditions as in the SR-OCSA test, an indentation test was conducted, and relaxation time was measured to evaluate the relationship between ACSR and relaxation time. RESULTS: SR-OCSA could nondestructively detect and visualize changes in the distribution of viscoelastic properties of articular cartilage in early osteoarthritis. SR-OCSA captured significant increases in ACSR in cartilage at 2 weeks after surgery, when a histologically slight osteoarthritis sign was present. As cartilage degeneration progressed, ACSR increased, whereas relaxation time decreased in a time-dependent manner. Moreover, ACSR negatively correlated with relaxation time. In particular, ACSR was elevated around the tidemark and the elevation tended to move as cartilage degeneration progressed. CONCLUSIONS: SR-OCSA could tomographically and nondestructively detect and visualize changes in the distribution of viscoelastic properties of articular cartilage in early osteoarthritis. The mechanical properties around the tidemark were degraded as cartilage degeneration progressed. Thus, SR-OCSA provides important data needed to understand the biomechanics of early osteoarthritis.


Assuntos
Cartilagem Articular/patologia , Articulação do Joelho/patologia , Osteoartrite do Joelho/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Animais , Ligamento Cruzado Anterior/cirurgia , Cartilagem Articular/diagnóstico por imagem , Modelos Animais de Doenças , Elasticidade , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Coelhos , Estresse Mecânico , Fatores de Tempo
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