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1.
Arthritis Res Ther ; 25(1): 3, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609338

RESUMO

Osteoarthritis (OA) is a common and prevalent degenerative joint disease characterized by degradation of the articular cartilage. However, none of disease-modifying OA drugs is approved currently. Teriparatide (PTH (1-34)) might stimulate chondrocyte proliferation and cartilage regeneration via some uncertain mechanisms. Relevant therapies of PTH (1-34) on OA with such effects have recently gained increasing interest, but have not become widespread practice. Thus, we launch this systematic review (SR) to update the latest evidence accordingly. A comprehensive literature search was conducted in PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase from their inception to February 2022. Studies investigating the effects of the PTH (1-34) on OA were obtained. The quality assessment and descriptive summary were made of all included studies. Overall, 307 records were identified, and 33 studies were included. In vivo studies (n = 22) concluded that PTH (1-34) slowed progression of OA by alleviating cartilage degeneration and aberrant remodeling of subchondral bone (SCB). Moreover, PTH (1-34) exhibited repair of cartilage and SCB, analgesic, and anti-inflammatory effects. In vitro studies (n = 11) concluded that PTH (1-34) was important for chondrocytes via increasing the proliferation and matrix synthesis but preventing apoptosis or hypertrophy. All included studies were assessed with low or unclear risk of bias in methodological quality. The SR demonstrated that PTH (1-34) could alleviate the progression of OA. Moreover, PTH (1-34) had beneficial effects on osteoporotic OA (OPOA) models, which might be a therapeutic option for OA and OPOA treatment.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Teriparatida/farmacologia , Teriparatida/uso terapêutico , Teriparatida/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Hipertrofia
2.
J Orthop Surg Res ; 18(1): 18, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609383

RESUMO

PURPOSE: The purpose of this study was to investigate the early outcomes of the new semi-constrained revision total knee arthroplasty (TKA) system by performing subgroup analysis according to the revision cause. MATERIALS AND METHODS: From August 2019 to July 2020, 83 revision TKAs using the fixed-bearing Attune® revision knee system with a minimum follow-up of 2 years were retrospectively reviewed. Clinically, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, the Western Ontario and McMaster Universities Osteoarthritis Index, and range of motion (ROM) were evaluated. The incidence of systemic and specific postoperative complications was investigated. Each cohort was divided into septic (group A, 34 patients) and aseptic mode (group B, 41 patients), and compared to assess the outcomes. RESULTS: The mean age at the time of revision was 73.3 years (range 59.0 to 84.0 years), and the follow-up duration was 36.1 months (range 30.0 to 40.0 months). Clinical outcomes and ROM significantly improved at last follow-up (p < 0.001). Group A showed statistically inferior clinical outcomes in the last follow-up compared to group B. Four knees (5.3%) had a postoperative femoral joint line elevation of more than 5 mm. There were no serious systemic complications. One patient underwent re-revision TKA due to recurrence of infection. No stem tip impingement or cortical erosion was observed in all patients. CONCLUSIONS: Revision TKAs using a new semi-constrained revision system showed favorable short-term follow-up outcomes, with improvement in clinical scores and ROM. Moreover, by using stem offsets, no postoperative stem tip impingement or cortical erosion was found. LEVEL OF EVIDENCE: Level IV, Retrospective Case Series.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Seguimentos , Prótese do Joelho/efeitos adversos , Desenho de Prótese , Reoperação , Articulação do Joelho/cirurgia , Osteoartrite/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento
3.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614257

RESUMO

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA.


Assuntos
Cartilagem Articular , MicroRNAs , Osteoartrite , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Condrócitos/metabolismo , Matriz Extracelular/metabolismo , Cartilagem Articular/metabolismo , Inflamação/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo
4.
Ann Med ; 55(1): 175-189, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36661308

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with an increased risk of death, but its underlying mechanisms are not fully understood. Circular RNAs (circRNAs) have recently been implicated in various biological processes. The aim of this study was to investigate the key circRNAs related to RA. METHODS: A microarray assay was used to identify the differentially expressed circRNAs (DEcircRNAs) in peripheral blood mononuclear cells (PBMCs) from patients with RA compared to patients with osteoarthritis (OA) and healthy controls. Then, quantitative real-time PCR was applied to verify the DEcircRNAs, and correlations between the levels of DEcircRNAs and laboratory indices were analysed. We also performed extensive bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway and potential circRNA-miRNA-mRNA network analyses to predict the function of these DEcircRNAs. RESULTS: A total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively. Nine out of the DEcircRNAs in RA were validated by real-time PCR. There were correlations between the levels of DEcircRNAs and some of the laboratory indices. GO analyses revealed that these DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, cell cycle, posttranslational protein modification and collagen formation. Functional annotation of host genes of these DEcircRNAs was implicated in several significantly enriched pathways, including metabolic pathways, ECM-receptor interaction, the PI3K-Akt signalling pathway, the AMPK signalling pathway, leukocyte transendothelial migration, platelet activation and the cAMP signalling pathway, which might be responsible for the pathophysiology of RA. CONCLUSIONS: The findings of this study may help to elucidate the role of circRNAs in the specific mechanism underlying RA.Key messagesMicroarray assays showed that a total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively.Nine out of the DEcircRNAs in RA were validated by real-time PCR, and the levels of the DEcircRNAs were related to some of the laboratory indices.GO analyses revealed that the DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, etc.Functional annotation of host genes of the DEcircRNAs in RA was implicated in several significantly enriched pathways, including metabolic pathways, ECM-receptor interaction, the PI3K-Akt signalling pathway, etc.


Assuntos
Artrite Reumatoide , MicroRNAs , Osteoartrite , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Leucócitos Mononucleares/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Perfilação da Expressão Gênica , MicroRNAs/genética , Artrite Reumatoide/genética , Osteoartrite/genética , Osteoartrite/metabolismo
5.
Int J Biol Sci ; 19(1): 13-33, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594090

RESUMO

Background: Chondrocyte hypertrophy has been implicated in endochondral ossification and osteoarthritis (OA). In OA, hypertrophic chondrocytes contribute to the destruction and focal calcification of the joint cartilage. Although studies in this field have remarkably developed the modulation of joint inflammation using gene therapy and regeneration of damaged articular cartilage using cell therapy, studies that can modulate or prevent hypertrophic changes in articular chondrocytes are still lacking. Methods: In vitro hypertrophic differentiation and inflammation assays were conducted using human normal chondrocyte cell lines, TC28a2 cells. Human cartilage tissues and primary articular chondrocytes were obtained from OA patients undergoing total knee arthroplasty. Long non-coding RNAs (lncRNAs), LINC02035 and LOC100130207, were selected through RNA-sequencing analysis using RNAs extracted from TC28a2 cells cultured in hypertrophic medium. The regulatory mechanism was evaluated using western blotting, real-time quantitative polymerase chain reaction, osteocalcin reporter assay, RNA-immunoprecipitation (RNA-IP), RNA-in situ hybridization, and IP. Results: LncRNAs are crucial regulators of various biological processes. In this study, we identified two important lncRNAs, LINC02035 and LOC100130207, which play important roles in hypertrophic changes in normal chondrocytes, through RNA sequencing. Interestingly, the expression level of RUNX2, a master regulator of chondrocyte hypertrophy, was regulated at the post-translational level during hypertrophic differentiation of the normal human chondrocyte cell line, TC28a2. RNA-immunoprecipitation proved the potential interaction between RUNX2 protein and both lncRNAs. Knockdown (KD) of LINC02035 or LOC100130207 promoted ubiquitin-mediated proteasomal degradation of RUNX2 and prevented hypertrophic differentiation of normal chondrocyte cell lines, whereas overexpression of both lncRNAs stabilized RUNX2 protein and generated hypertrophic changes. Furthermore, the KD of the two lncRNAs mitigated the destruction of important cartilage matrix proteins, COL2A1 and ACAN, by hypertrophic differentiation or inflammatory conditions. We also confirmed that the phenotypic changes raised by the two lncRNAs could be rescued by modulating RUNX2 expression. In addition, the KD of these two lncRNAs suppressed hypertrophic changes during chondrogenic differentiation of mesenchymal stem cells. Conclusion: Therefore, this study suggests that LINC02035 and LOC100130207 contribute to hypertrophic changes in normal chondrocytes by regulating RUNX2, suggesting that these two novel lncRNAs could be potential therapeutic targets for delaying or preventing OA development, especially for preventing chondrocyte hypertrophy.


Assuntos
Cartilagem Articular , Osteoartrite , RNA Longo não Codificante , Humanos , Condrócitos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Hipertrofia/metabolismo , Osteoartrite/genética , Diferenciação Celular/genética , Inflamação/metabolismo
6.
J Zoo Wildl Med ; 53(4): 801-810, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36640083

RESUMO

Osteoarthritis (OA) is common in zoo Asian (Elephas maximus) and African (Loxodonta africana) elephants. This study investigated the relationship between confirmed or suspected OA with ovarian cyclicity, gonadotropins, progestagens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and collagen type I (CTX-I) in zoo elephants. In Asian elephants, odds of having confirmed or suspected OA decreased with cycling (OR = 0.22, P = 0.016; OR = 0.29, P = 0.020, respectively), however, not when adjusted for age (odds ratio [OR] = 0.31, P = 0.112; OR = 0.58, P = 0.369, respectively). In African elephants, none of the models between confirmed OA and cycling status were significant (P > 0.060), while the odds of having suspected OA decreased with cycling (OR = 0.12, P = 0.001), even after adjusting for age (OR = 0.15, P = 0.005). Progestagens (Asian elephants P > 0.096; African elephants P > 0.415), LH (Asian P > 0.129; African P > 0.359), and FSH (Asian P > 0.738; African P > 0.231) did not differ with confirmed or suspected OA status, unadjusted. CTX-I concentrations were not related to OA status (P > 0.655). This study concluded hormonal changes may not have a strong impact on OA, so additional investigation into other serologic biomarkers is warranted.


Assuntos
Elefantes , Osteoartrite , Animais , Progestinas , Hormônio Luteinizante , Hormônio Foliculoestimulante , Osteoartrite/veterinária , Animais de Zoológico
7.
BMC Musculoskelet Disord ; 24(1): 31, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639624

RESUMO

BACKGROUND: Total knee and hip arthroplasty are considered a clinically and cost-effective intervention, however, persistent pain post-surgery can occur, and some continue to take opioid medications long-term. One factor which has infrequently been included in prediction modelling is rehabilitation pathway, in particular, one which includes inpatient rehabilitation. As discharge to inpatient rehabilitation post-arthroplasty is common practice, we aimed to identify whether rehabilitation pathway (discharge to in-patient rehabilitation or not) predicts continued use of opioids at 3 months (90 days) post- total knee arthroplasty (TKA) and total hip arthroplasty (THA) whilst controlling for other covariates. METHODS: The study was nested within a prospective observational study capturing pre-operative, acute care and longer-term data from 1900 osteoarthritis (OA) patients who underwent primary TKA or THA. The larger study involved a part-random, part-convenience sample of 19 high-volume hospitals across Australia. Records with complete pre-and post-operative analgesic (35 days and 90 days) use were identified [1771 records (93% of sample)] and included in logistic regression analyses. RESULTS: Three hundred and thirteen people (17.8%) reported ongoing opioid use at 90 days post-operatively. In the adjusted model, admission to inpatient rehabilitation after surgery was identified as an independent and significant predictor of opioid use at 90-days. Inpatient rehabilitation was associated with almost twice the odds of persistent opioid use at 90-days compared to discharge directly home (OR = 1.9 (1.4, 2.5), p < .001). CONCLUSION: The inpatient rehabilitation pathway is a strong predictor of longer-term opioid use (90 days) post-arthroplasty, accounting for many known and possible confounders of use including sex, age, insurance status, major complications, smoking status and baseline body pain levels. TRIAL REGISTRATION: The study was nested within a prospective cohort observational study capturing pre-operative, acute-care and longer-term data from patients undergoing primary TKA or THA for osteoarthritis (ClinicalTrials.gov NCT01899443).


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Transtornos Relacionados ao Uso de Opioides , Osteoartrite , Humanos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/reabilitação , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/reabilitação , Analgésicos Opioides/uso terapêutico , Estudos Prospectivos , Alta do Paciente , Pacientes Internados , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia
8.
J Orthop Trauma ; 37(2): e68-e72, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36658698

RESUMO

OBJECTIVES: We report our clinical results following surgical intervention for capitellar fractures in a pediatric population, highlighting approaches, surgical instruments, and possible prognostic factors. DESIGN: Retrospective descriptive case-series study. SETTING: A tertiary referral hospital. PATIENTS: Twelve pediatric patients with capitellar or capitellar-trochlear injuries were treated between 2017 and 2021. INTERVENTION: Open reduction and internal fixation primarily using cannulated headless screws. MAIN OUTCOME MEASUREMENTS: The mean follow-up period was 22 months (range: 10-35 months). Functional outcomes were assessed using the Mayo Elbow Performance Score. Post-traumatic elbow arthrosis was assessed using the Bromberg and Morrey rating system. RESULTS: All fractures healed within 5-7 weeks. The mean Mayo Elbow Performance Score value was 98 (range, 85-100). Three patients developed arthrosis, and one had capitellar osteonecrosis. CONCLUSIONS: Based on our experience, the Kocher approach and fixation of 2-3 retrograde cannulated screws together represent an appropriate surgical technique for isolated capitellar fractures, whereas good functional outcomes are attainable for capitellar-trochlear shear fractures using the transolecranon approach with 3 cannulated screw fixations. Further injuries to the osseoligamentous structures around the elbow joint are suspected to be an unfavorable prognostic factor. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Articulação do Cotovelo , Fraturas do Úmero , Osteoartrite , Humanos , Criança , Estudos Retrospectivos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Articulação do Cotovelo/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento
9.
Sci Rep ; 13(1): 1124, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670151

RESUMO

Osteoarthritis (OA) is the most prevalent joint disorder with increasing worldwide incidence. Mechanistic insights into OA pathophysiology are evolving and there are currently no disease-modifying OA drugs. An increase in protease activity is linked to progressive degradation of the cartilage in OA. Proteases also trigger inflammation through a family of G protein-coupled receptors (GPCRs) called the Proteinase-Activated Receptors (PARs). PAR signaling can trigger pro-inflammatory responses and targeting PARs is proposed as a therapeutic approach in OA. Several enzymes can cleave the PAR N-terminus, but the endogenous protease activators of PARs in OA remain unclear. Here we characterized PAR activating enzymes in knee joint synovial fluids from OA patients and healthy donors using genetically encoded PAR biosensor expressing cells. Calcium signaling assays were performed to examine receptor activation. The class and type of enzymes cleaving the PARs was further characterized using protease inhibitors and fluorogenic substrates. We find that PAR1, PAR2 and PAR4 activating enzymes are present in knee joint synovial fluids from healthy controls and OA patients. Compared to healthy controls, PAR1 activating enzymes are elevated in OA synovial fluids while PAR4 activating enzyme levels are decreased. Using enzyme class and type selective inhibitors and fluorogenic substrates we find that multiple PAR activating enzymes are present in OA joint fluids and identify serine proteinases (thrombin and trypsin-like) and matrix metalloproteinases as the major classes of PAR activating enzymes in the OA synovial fluids. Synovial fluid driven increase in calcium signaling was significantly reduced in cells treated with PAR1 and PAR2 antagonists, but not in PAR4 antagonist treated cells. OA associated elevation of PAR1 cleavage suggests that targeting this receptor may be beneficial in the treatment of OA.


Assuntos
Osteoartrite , Receptor PAR-1 , Humanos , Receptor PAR-1/metabolismo , Líquido Sinovial/metabolismo , Corantes Fluorescentes , Trombina/metabolismo , Receptor PAR-2/metabolismo
10.
Arthroscopy ; 39(2): 358-359, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36604002

RESUMO

When we are looking at the stars, we are in fact looking back in time. This is because it takes years for the light from the stars to reach us. In similar fashion, when we are evaluating data on osteoarthritis after patellofemoral surgery, we need to consider what kind of procedure was performed. Furthermore, it is extremely important to answer the question of whether the patellofemoral instability itself or the surgical procedure is causing the arthritis. Recent evidence suggests that recurrent patellofemoral instability is causing cartilage degeneration and stopping this process via surgical restoration of the anatomy and biomechanics of the patellofemoral joint may significantly reduce the risk of osteoarthritis. Shear loading of the cartilage can be detrimental. An instability event elicits inflammatory markers that are shown to induce arthritis. On the other hand, there is the argument that over-constraint may lead to arthritis owing to an increase in cartilage loading. Another argument is that surgery may not fully restore the patellofemoral anatomy. Appropriate patient selection and continuous evolution of our surgical procedures are key elements toward successful management of patellofemoral instability.


Assuntos
Doenças das Cartilagens , Instabilidade Articular , Osteoartrite , Articulação Patelofemoral , Humanos , Articulação Patelofemoral/cirurgia , Articulação Patelofemoral/anatomia & histologia , Cartilagem , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia
11.
Trials ; 24(1): 24, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635747

RESUMO

BACKGROUND: Osteoarthritis (OA) affects 20% of the adult Danish population, and the financial burden to society amounts to DKK 4.6 billion annually. Research suggests that up to 75% of surgical patients could have postponed an operation and managed with physical training. ERVIN.2 is an artificial intelligence (AI)-based clinical support system that addresses this problem by enhancing patient involvement in decisions concerning surgical knee and hip replacement. However, the clinical outcomes and cost-effectiveness of using such a system are scantily documented. OBJECTIVE: The primary objective is to investigate whether the usual care is non-inferior to ERVIN.2 supported care. The second objective is to determine if ERVIN.2 enhances clinical decision support and whether ERVIN.2 supported care is cost-effective. METHODS: This study used a single-centre, non-inferiority, randomised controlled in a two-arm parallel-group design. The study will be reported in compliance with CONSORT guidelines. The control group receives the usual care. As an add-on, the intervention group have access to baseline scores and predicted Oxford hip/knee scores and HRQoL for both the surgical and the non-surgical trajectory. A cost-utility analysis will be conducted alongside the trial using a hospital perspective, a 1-year time horizon and effects estimated using EQ-5D-3L. Results will be presented as cost per QALY gain. DISCUSSION: This study will bring knowledge about whether ERVIN.2 enhances clinical decision support, clinical effects, and cost-effectiveness of the AI system. The study design will not allow for the blinding of surgeons. TRIAL REGISTRATION: ClinicalTrials.gov NCT04332055 . Registered on 2 April 2020.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Osteoartrite , Adulto , Humanos , Inteligência Artificial , Articulação do Joelho/cirurgia , Análise Custo-Benefício , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Arthritis Res Ther ; 25(1): 7, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635774

RESUMO

BACKGROUND: Hypertension is a common comorbidity of osteoarthritis (OA) with known autonomic dysregulation; thus, the autonomic nervous system may provide a shared underlying mechanism. The objective of this study was to examine the role of the autonomic nervous system in a preclinical model of OA and hypertension. METHODS: Experiments were conducted in spontaneously hypertensive rats and a normotensive control strain, including male and female rats. OA was surgically induced via medial meniscus transection with skin incision used as a sham control (n = 7-8/strain/sex/surgery). Tactile sensitivity, anxiety-related behavior, and serum corticosterone were measured at baseline then bi-weekly across 8 weeks. At weeks 9-10, cardiovascular responses to a chemical vagal nerve agonist were determined to indirectly evaluate vagus nerve function. The joint structure was assessed via grading of histological sections. RESULTS: In males, OA resulted in thinner cartilage in both hypertensive (OA vs. non-OA p < 0.001) and normotensive (OA vs. non-OA p < 0.001). Only females with comorbid hypertension and OA displayed thinner cartilage (p = 0.013). Male hypertensive OA animals had increased calcified subchondral bone compared to normotensive OA animals (p = 0.043) while female hypertensive OA animals had increased calcified subchondral bone compared to hypertensive sham animals (p < 0.001). All MCLT+MMT groups developed low-grade synovitis; interestingly, hypertensive OA females had higher synovitis scores than normotensive OA females (p = 0.046). Additionally, hypertension led to larger drops in blood pressure with vagal activation in both OA (hypertensive vs. normotensive p = 0.018) and sham (hypertensive vs. normotensive p < 0.001) male animals. In females, this trend held true only in OA animals (normotensive vs. hypertensive p = 0.005). CONCLUSION: These data provide preliminary evidence that hypertension influences OA progression and encourages further study into the autonomic nervous system as a possible mechanism.


Assuntos
Cartilagem Articular , Hipertensão , Osteoartrite , Sinovite , Ratos , Masculino , Feminino , Animais , Osteoartrite/patologia , Meniscos Tibiais , Osso e Ossos , Sinovite/patologia , Modelos Animais de Doenças , Cartilagem Articular/patologia
13.
FASEB J ; 37(2): e22746, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36622202

RESUMO

In osteoarthritis (OA), chondrocytes undergo many pathological alternations that are linked with cellular senescence. However, the exact pathways that lead to the generation of a senescence-like phenotype in OA chondrocytes are not clear. Previously, we found that loss of estrogen receptor-α (ERα) was associated with an increased senescence level in human chondrocytes. Since DNA damage is a common cause of cellular senescence, we aimed to study the relationship among ERα levels, DNA damage, and senescence in chondrocytes. We first examined the levels of ERα, representative markers of DNA damage and senescence in normal and OA cartilage harvested from male and female human donors, as well as from male mice. The influence of DNA damage on ERα levels was studied by treating human chondrocytes with doxorubicin (DOX), which is an often-used DNA-damaging agent. Next, we tested the potential of overexpressing ERα in reducing DNA damage and senescence levels. Lastly, we explored the interaction between ERα and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Results indicated that the OA chondrocytes contained DNA damage and displayed senescence features, which were accompanied by significantly reduced ERα levels. Overexpression of ERα reduced the levels of DNA damage and senescence in DOX-treated normal chondrocytes and OA chondrocytes. Moreover, DOX-induced the activation of NF-κB pathway, which was partially reversed by overexpressing ERα. Taken together, our results demonstrated the critical role of ERα in maintaining the health of chondrocytes by inhibiting DNA damage and senescence. This study also suggests that maintaining the ERα level may represent a new avenue to prevent and treat OA.


Assuntos
Condrócitos , Osteoartrite , Masculino , Humanos , Feminino , Camundongos , Animais , Condrócitos/metabolismo , NF-kappa B/metabolismo , Receptores de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Ligantes , Osteoartrite/metabolismo , Senescência Celular/fisiologia , Dano ao DNA
14.
Cancer Control ; 30: 10732748221150393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36631419

RESUMO

BACKGROUND: Multimorbidity is a concern for people living with cancer, as over 90% have at least one other condition. Multimorbidity complicates care coming from multiple providers who work within separate, siloed systems. Information describing high-risk and high-cost disease combinations has potential to improve the experience, outcome, and overall cost of care by informing comprehensive care management frameworks. This study aimed to identify disease combinations among people with cancer and other conditions, and to assess the health burden associated with those combinations to help healthcare providers more effectively prioritize and coordinate care. METHODS: We used a population-based retrospective cohort design including adults with a cancer diagnosis between March-2003 and April-2013, followed-up until March 2018. We used observed disease combinations defined by level of multimorbidity and partitive (k-means) clusters, ie groupings of similar diseases based on the prevalence of each condition. We assessed disease combination-associated health burden through health service utilization, including emergency department visits, primary care visits and hospital admissions during the follow-up period. RESULTS: 549,248 adults were included in the study. Anxiety, diabetes mellitus, hypertension, and osteoarthritis co-occurred with cancer 1.1 to 5.3 times more often than expected by chance. Disease combinations varied by cancer type and age but were similar between sexes. The largest partitive cluster included cancer and anxiety, with at least 25% of individuals also having osteoarthritis. Cancer also tended to co-occur with hypertension (8.0%) or osteoarthritis (6.2%). There were differences between clusters in healthcare utilization, regardless of the number of disease combinations or clustering approach used. CONCLUSION: Researchers, clinicians, policymakers, and other stakeholders can use the clustering information presented here to improve the healthcare system for people with cancer multimorbidity by developing cluster-specific care management and clinical guidelines for common disease combinations.


Assuntos
Hipertensão , Neoplasias , Osteoartrite , Adulto , Humanos , Multimorbidade , Estudos Retrospectivos , Comorbidade , Ontário/epidemiologia , Doença Crônica , Hipertensão/epidemiologia , Osteoartrite/epidemiologia , Neoplasias/epidemiologia , Neoplasias/terapia , Análise por Conglomerados
15.
J Orthop Surg Res ; 18(1): 34, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635778

RESUMO

OBJECTIVE: This study aims to investigate the correlation of long non-coding RNA HOX transcript antisense RNA (lncRNA HOTAIR) with the PTEN/PI3K/AKT pathway and clinical-related indicators in osteoarthritis (OA) and determine the effect of baicalin intervention. METHODS: The levels of clinical lipid metabolism indexes and immune-inflammatory indexes in OA patients and normal controls was detected. OA chondrocytes (OA-CHs) were induced with peripheral blood mononuclear cells (PBMCs), followed by baicalin treatment (50 ug/mL). RT-qPCR was performed to measure lncRNA HOTAIR expression. The levels of inflammatory cytokines and adiponectin were detected using ELISA kits. CCK-8 assay was used to assess the viability of CHs. The related protein expression was measured using Western blot analysis. RESULTS: LncRNA HOTAIR might act as a biomarker of OA in vivo. LncRNA HOTAIR was positively correlated with TC, hs-CRP, IgA, TNF-α, and VAS score. Overexpression of lncRNA HOTAIR in vitro inhibited cell proliferation, reduced IL-10 and PTEN expression, but augmented TNF-α, p-PI3K, and p-AKT proteins in OA-CHs stimulated by OA-PBMCs. The changes of above indexes were also observed in OA-CHs stimulated by OA-PBMCs treated with si-lncRNA HOTAIR or baicalin, implying the synergistic effects of baicalin and lncRNA HOTAIR silencing on OA. CONCLUSIONS: Conclusively, lncRNA HOTAIR was highly expressed in OA-CHs, which facilitated OA inflammatory responses by orchestrating inflammatory cytokines and the PTEN/PI3K/AKT pathway. Baicalin exerted therapeutic effects by inhibiting the expression of lncRNA HOTAIR, decreasing the protein levels of p-PI3K and p-AKT, and increasing the protein levels of PTEN, APN, and ADIPOR1.


Assuntos
Osteoartrite , RNA Longo não Codificante , Humanos , Apoptose/genética , Condrócitos/metabolismo , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Osteoartrite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
J Orthop Surg Res ; 18(1): 41, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647153

RESUMO

OBJECTIVE: To identify primary Sjögren's syndrome (pSS) patients with arthralgia at risk for osteoarthritis (OA) or arthritis. METHODS: This study included 368 pSS patients admitted to a mono-centric from March 2010 to December 2020. Patients were divided into groups according to whether complicated with OA or arthritis. Data were analyzed to determine the differences in demographical characteristics, symptoms, and laboratory examination. RESULTS: The involvement of the OA joints was predominately knee and spine sites (including cervical and lumbar spine degeneration). When diagnosing arthritis, it was mainly peripheral symmetric polyarthritis, the most affected sites were the interphalangeal and metacarpophalangeal joints. There were significant differences in age, disease duration, uric acid (UA), and total cholesterol (TC) between pSS-OA and pSS-nOA patients (P < 0.050). Logistic regression analysis showed that age (OR = 1.965; P = 0.009) and joint pain (OR = 3.382; P < 0.001) were dangerous factors associated with OA. Interestingly, although the level of UA, TC, and triglycerides (TG) was shown to be positive with OA, there was no statistical significance after the OR was computed in the four-cell table. In pSS-arthritis, EULAR Sjögren's syndrome disease activity index (ESSDAI) (P = 0.011), the frequency of joint pain (P < 0.001), and muscular involvement (P = 0.037) were higher than non-arthritis group. In pSS patients only presenting with joint pain, arthritis patients had higher ESSDAI and system involvements, but lower UA and TG levels compared with OA group (P < 0.050). CONCLUSION: In pSS patients with arthralgia, OA accounted for the majority. pSS patients with advanced age and more pronounced metabolic characteristics, such as elevated blood lipids and uric acid, was a key factor in groups at risk for OA. However, arthritis patients had higher rates of dry mouth and eye, higher disease activity, antibodies positive, and more organs damage. In the future, it may be necessary to be more cautious in the diagnosis of joint manifestations in pSS patients in order to make the appropriate treatments.


Assuntos
Osteoartrite , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Ácido Úrico , Osteoartrite/complicações , Artralgia/diagnóstico , Artralgia/etiologia , Articulação Metacarpofalângica
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 49-53, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647642

RESUMO

Osteoarthritis (OA) is the most common type of arthritis. The prevalence and the incidence of OA have been continuously growing along with increased life expectancy and the emerging problem of an aging population around the global. Reported findings have confirmed that osteoarthritis is a chronic inflammatory disease and its major risk factors included genetic susceptibility, aging, and environmental factors. However, the pathogenic mechanisms of osteoarthritis remain unclear. Recent studies have shown that oral-gut microbes are associated with the onset and development of osteoarthritis and may provide new targets for osteoarthritis treatment. Herein, we reviewed the latest developments in research on the relationship between oral-gut microbes and the onset and development of osteoarthritis, with a view to creating new perspectives for further elucidation of the pathogenesis of osteoarthritis and exploration of effective treatments in the future.


Assuntos
Microbioma Gastrointestinal , Osteoartrite , Humanos , Idoso , Osteoartrite/etiologia , Osteoartrite/patologia , Envelhecimento , Incidência , Prevalência
19.
Arthritis Res Ther ; 25(1): 6, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627721

RESUMO

OBJECTIVE: Platelet-rich plasma (PRP) therapy is increasingly popular to treat musculoskeletal diseases, including tendinopathies and osteoarthritis (OA). To date, it remains unclear to which extent PRP compositions are determined by the immune cell and cytokine profile of individuals or by the preparation method. To investigate this, we compared leukocyte and cytokine distributions of different PRP products to donor blood samples and assessed the effect of pro-inflammatory cytokines on chondrocytes. DESIGN: For each of three PRP preparations (ACP®, Angel™, and nSTRIDE® APS), products were derived using whole blood samples from twelve healthy donors. The cellular composition of PRP products was analyzed by flow cytometry using DURAClone antibody panels (DURAClone IM Phenotyping Basic and DURAClone IM T Cell Subsets). The MESO QuickPlex SQ 120 system was used to assess cytokine profiles (V-PLEX Proinflammatory Panel 1 Human Kit, Meso Scale Discovery). Primary human chondrocyte 2D and 3D in vitro cultures were exposed to recombinant IFN-γ and TNF-α. Proliferation and chondrogenic differentiation were quantitatively assessed. RESULTS: All three PRP products showed elevated portions of leukocytes compared to baseline levels in donor blood. Furthermore, the pro-inflammatory cytokines IFN-γ and TNF-α were significantly increased in nSTRIDE® APS samples compared to donor blood and other PRP products. The characteristics of all other cytokines and immune cells from the donor blood, including pro-inflammatory T cell subsets, were maintained in all PRP products. Chondrocyte proliferation was impaired by IFN-γ and enhanced by TNF-α treatment. Differentiation and cartilage formation were compromised upon treatment with both cytokines, resulting in altered messenger ribonucleic acid (mRNA) expression of collagen type 1A1 (COL1A1), COL2A1, and aggrecan (ACAN) as well as reduced proteoglycan content. CONCLUSIONS: Individuals with elevated levels of cells with pro-inflammatory properties maintain these in the final PRP products. The concentration of pro-inflammatory cytokines strongly varies between PRP products. These observations may help to unravel the previously described heterogeneous response to PRP in OA therapy, especially as IFN-γ and TNF-α impacted primary chondrocyte proliferation and their characteristic gene expression profile. Both the individual's immune profile and the concentration method appear to impact the final PRP product. TRIAL REGISTRATION: This study was prospectively registered in the Deutsches Register Klinischer Studien (DRKS) on 4 November 2021 (registration number DRKS00026175).


Assuntos
Osteoartrite , Plasma Rico em Plaquetas , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Condrócitos/metabolismo , Citocinas/metabolismo , Osteoartrite/terapia , Osteoartrite/metabolismo , Plasma Rico em Plaquetas/metabolismo
20.
Int J Biol Sci ; 19(2): 675-690, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632459

RESUMO

Pain is the major reason that patients suffering from osteoarthritis (OA) seek medical care. We found that vascular endothelial growth factors (VEGFs) mediate signaling in OA pain pathways. To determine the specific contributions of VEGFs and their receptors (VEGFRs) to joint pathology and pain transmission during OA progression, we studied intra-articular (IA) injections of VEGF ligands into murine knee joints. Only VEGF ligands specific for the activation of VEGFR1, but not VEGFR2, induced allodynia within 30 min. Interventions in OA by inhibitors of VEGFRs were done in vivo using a preclinical murine OA model by IA injections of selective inhibitors of VEGFR1/VEGFR2 kinase (pazopanib) or VEGFR2 kinase (vandetanib). OA phenotypes were evaluated using pain-associated murine behavioral tests and histopathologic analyses. Alterations in VEGF/VEGFR signaling by drugs were determined in knee joints, dorsal root ganglia, and spinal cord by immunofluorescence microscopy. Pazopanib immediately relieved OA pain by interfering with pain transmission pathways. Pain reduction by vandetanib was mainly due to the inhibition of cartilage degeneration by suppressing VEGFR2 expression. In conclusion, IA administration of pazopanib, which simultaneously inhibits VEGFR1 and VEGFR2, can be developed as an ideal OA disease-modifying drug that rapidly reduces joint pain and simultaneously inhibits cartilage degeneration.


Assuntos
Osteoartrite , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Dor/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Fatores de Crescimento do Endotélio Vascular/uso terapêutico
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