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1.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360594

RESUMO

Glucocorticoids provide indispensable anti-inflammatory therapies. However, metabolic adverse effects including muscle wasting restrict their use. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) modulates peripheral glucocorticoid responses through pre-receptor metabolism. This study investigates how 11ß-HSD1 influences skeletal muscle responses to glucocorticoid therapy for chronic inflammation. We assessed human skeletal muscle biopsies from patients with rheumatoid arthritis and osteoarthritis for 11ß-HSD1 activity ex vivo. Using the TNF-α-transgenic mouse model (TNF-tg) of chronic inflammation, we examined the effects of corticosterone treatment and 11ß-HSD1 global knock-out (11ßKO) on skeletal muscle, measuring anti-inflammatory gene expression, muscle weights, fiber size distribution, and catabolic pathways. Muscle 11ß-HSD1 activity was elevated in patients with rheumatoid arthritis and correlated with inflammation markers. In murine skeletal muscle, glucocorticoid administration suppressed IL6 expression in TNF-tg mice but not in TNF-tg11ßKO mice. TNF-tg mice exhibited reductions in muscle weight and fiber size with glucocorticoid therapy. In contrast, TNF-tg11ßKO mice were protected against glucocorticoid-induced muscle atrophy. Glucocorticoid-mediated activation of catabolic mediators (FoxO1, Trim63) was also diminished in TNF-tg11ßKO compared to TNF-tg mice. In summary, 11ß-HSD1 knock-out prevents muscle atrophy associated with glucocorticoid therapy in a model of chronic inflammation. Targeting 11ß-HSD1 may offer a strategy to refine the safety of glucocorticoids.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Artrite Reumatoide/tratamento farmacológico , Deleção de Genes , Glucocorticoides/efeitos adversos , Atrofia Muscular/prevenção & controle , Osteoartrite do Quadril/tratamento farmacológico , Animais , Artrite Reumatoide/patologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/genética , Atrofia Muscular/patologia , Osteoartrite do Quadril/patologia
2.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201564

RESUMO

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.


Assuntos
Cartilagem Articular/patologia , Citocinas/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Osteoartrite do Quadril/metabolismo , Idoso , Idoso de 80 Anos ou mais , Cartilagem Articular/metabolismo , Quimiocinas/metabolismo , Condrócitos/metabolismo , Citocinas/sangue , Articulação do Quadril/metabolismo , Articulação do Quadril/fisiopatologia , Humanos , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinases da Matriz/metabolismo , Pessoa de Meia-Idade , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/sangue , Obesidade/metabolismo , Técnicas de Cultura de Órgãos , Osteoartrite do Quadril/patologia , Proteoglicanas/metabolismo
3.
Res Vet Sci ; 137: 243-251, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34049111

RESUMO

The development and early morphological features of feline hip osteoarthritis (OA) are largely unknown. Tears in the acetabular labrum and at the chondrolabral transition zone are suggested to be important in the pathogenesis of human hip OA, but in cats such lesions have not been described. We investigated associations between computed tomography (CT)-detected joint changes and microscopic articular cartilage lesions, the distribution of detected changes, and histologically evaluated the acetabular margin (AM) in hip joints from 20 cats. Histologic evaluation was undertaken on at least one joint from each cat. CT-detected joint changes and articular cartilage lesions were graded and the histological appearance of CT-detected osteophytes evaluated. The majority of CT-detected lesions and cartilage lesions were mild. Whole-joint CT scores and AM osteophyte CT scores showed moderate to strong correlation with cartilage scores. The odds were higher for presence of CT-detected osteophytes in craniodorsal, cranial, cranioventral, ventral and dorsal AM regions. Peripheral acetabular regions showed higher cartilage lesion grades than central regions. Tears, seen as fissures/clefts, in labral and perilabral tissues were common. CT-detected AM osteophytes morphologically presented as pointed sclerotic bone, spur-shaped bone or rounded chondro-osteophytes. The results suggest that CT is a valuable tool for diagnosing early feline hip OA. CT-detected osteophytes showed variable histologic morphologies, which may implicate different disease mechanisms and/or disease stages. Tears in the AM could represent an early event in feline hip OA and this warrants further investigation.


Assuntos
Acetábulo/patologia , Doenças do Gato/patologia , Articulação do Quadril/patologia , Osteoartrite do Quadril/veterinária , Animais , Cartilagem Articular/patologia , Doenças do Gato/diagnóstico por imagem , Gatos , Estudos Transversais , Feminino , Masculino , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/patologia , Tomografia Computadorizada por Raios X
4.
Front Immunol ; 12: 628654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692802

RESUMO

Dysregulation of circular RNAs (circRNAs) is involved in various human diseases. Fibroblast-like synoviocytes (FLSs), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype and contribute to joint destruction in rheumatoid arthritis (RA). In the present study, we identified a novel circRNA, Circ_0088194, which was upregulated in RA fibroblast-like synoviocytes (RA-FLSs) and correlated with the disease activity score in 28 joints. Overexpression of Circ_0088194 promoted RA-FLS migration and invasion, while inhibition of Circ_0088194 had the opposite effect. Mechanistically, Circ_0088194 acted as a miR-766-3p sponge to relieve the repressive effect of miR-766-3p on its target, MMP2 (encoding matrix metalloproteinase 2), thereby promoting migration and invasion. The expression level of Circ_0088194 was inversely correlated with that of miR-766-3p in RA-FLSs. Importantly, overexpression of miR-766-3p partially blocked the migration and invasion induced by Circ_0088194 overexpression. Collectively, this study identified a novel circRNA Circ_0088194 that promotes RA-FLS invasion and migration via the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA.


Assuntos
Artrite Reumatoide/metabolismo , Movimento Celular , Fibroblastos/metabolismo , Articulação do Quadril/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/metabolismo , Osteoartrite do Quadril/metabolismo , RNA Circular/metabolismo , Sinoviócitos/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Células Cultivadas , Feminino , Fibroblastos/patologia , Regulação da Expressão Gênica , Articulação do Quadril/patologia , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Osteoartrite do Quadril/genética , Osteoartrite do Quadril/patologia , Fenótipo , RNA Circular/genética , Transdução de Sinais , Sinoviócitos/patologia
5.
PLoS One ; 16(3): e0248767, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735210

RESUMO

OBJECTIVE: This study aimed to compare the symmetry of clinical and radiographic signs of right and left pelvic limbs of dogs with bilateral hip osteoarthritis (OA) and evaluate the association of physical findings and radiographic abnormalities. PATIENTS AND METHODS: One hundred pelvic limbs of police working dogs with bilateral hip OA were evaluated, following a screening program. Weight distribution, joint range of motion at flexion and extension, thigh girth, and radiographic signs were recorded and compared with the results of the contralateral limb and by breed, age, and sex with the Paired Samples T-Test and Pearson correlation coefficient, with p<0.05. RESULTS: The sample mean age was 6.5±2.2 years, and the bodyweight of 26.7±5.3kg. No significant differences were observed when comparing weight distribution, joint range of motion, and thigh girth of left and right limbs. Weight distribution and age showed a statistically significant correlation with joint extension. The right limbs showed a significantly higher frequency of circumferential femoral head osteophyte (CFHO) regarding radiographic signs. Limbs with CFHO or caudolateral curvilinear osteophyte had significantly larger joint flexion angle (p = 0.02) and smaller extension angle (p<0.01), respectively, compared to those that did not. Age showed a significant correlation with the presence of several radiographic findings, as did different breeds. CONCLUSION: Clinical and radiographic signs occur symmetrically in naturally occurring hip OA in police working dogs. Several correlations were observed between the evaluations performed and differences between breeds, which can be useful in assessing and early diagnosis of hip OA.


Assuntos
Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/veterinária , Cães Trabalhadores/fisiologia , Animais , Cruzamento , Cães , Feminino , Masculino , Osteoartrite do Quadril/patologia , Osteófito/diagnóstico por imagem , Pelve/diagnóstico por imagem
6.
Can J Surg ; 63(6): E537-E541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211642

RESUMO

BACKGROUND: Many practices require tissues from hip and knee arthroplasty procedures to be sent for pathologic examination. These examinations rarely provide information beyond the clinical or radiologic diagnosis and rarely alter clinical management. We aimed to determine the rate at which histologic diagnoses based on gross assessment alone or gross plus microscopic assessment correspond with reported clinical diagnoses in patients undergoing total joint arthroplasties and whether the histologic diagnoses alter patient management. METHODS: We retrospectively reviewed arthroplasty cases performed at a high-volume teaching hospital in Manitoba, Canada. The clinical diagnosis was compared with the final pathology report based on gross examination, with or without histologic assessment. The results of the comparison were classified into 3 categories: concordant (same diagnosis), discrepant (different diagnoses without alterations in management) and discordant (different diagnoses resulting in management change). The overall provincial cost for pathologic examination was determined by multiplying the total examination cost by the estimated number of arthroplasty cases. RESULTS: There were 773 patients in our study sample. The concordant rate was 98.3% (95% confidence interval [CI] 97.1%-99.1%), the discrepant rate was 1.7% (95% CI 0.9%-2.9%) and the discordant rate was 0.0% (95% CI 0%-0.5%) for 773 cases. The pathology diagnosis did not alter patient management in any case. A total of 91.5% of specimens did not require full histologic review and received gross descriptions only. The discrepancy rate was higher in cases that included microscopic examination than in those that received only gross descriptions (15.2% v. 0.4%, p < 0.001). The overall provincial cost for pathologic examination was estimated at Can$304 556. CONCLUSION: Submitting routine tissue from arthroplasty procedures to pathology does not affect patient management and therefore provides no value for the health care resources expended in doing so.


Assuntos
Artroplastia de Quadril/normas , Artroplastia do Joelho/normas , Técnicas Histológicas/normas , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Joelho/diagnóstico , Artroplastia de Quadril/economia , Artroplastia do Joelho/economia , Tomada de Decisão Clínica/métodos , Análise Custo-Benefício , Articulação do Quadril/patologia , Articulação do Quadril/cirurgia , Técnicas Histológicas/economia , Humanos , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Manitoba , Osteoartrite do Quadril/etiologia , Osteoartrite do Quadril/patologia , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Estudos Retrospectivos
7.
J Bone Joint Surg Am ; 102(Suppl 2): 3-7, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-32947596

RESUMO

Prearthritic hip disease is challenging to define, diagnose, and treat. The mechanically abnormal hip, which has not yet suffered irreversible damage but will do so if its abnormal mechanics are not corrected, can be considered to be in a prearthritic stage. A conundrum regarding the treatment of many patients with a variety of hip diseases involving a hip at mechanical risk is that the best opportunity for preventing progressive osteoarthritis lies in the period before symptoms are severe enough to demand treatment solely on that basis. It is difficult to institute treatment for a minimally symptomatic but at-risk hip because of the multitude of variables that affect symptoms and hip longevity. Input from an established team of multiple hip experts with varying areas of expertise is ideal. Shared decision-making is highly effective in this prearthritic situation of high patient sensitivity. The cornerstone of treatment of the prearthritic hip is the correction of the problematic mechanical abnormality. As methods of analysis and treatment methods evolve and as long-term outcomes of treatments become understood, the role of intervention during the prearthritic stage of hip disease is likely to increase.


Assuntos
Osteoartrite do Quadril/diagnóstico , Quadril/patologia , Quadril/fisiopatologia , Quadril/cirurgia , Humanos , Osteoartrite do Quadril/patologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Quadril/cirurgia , Sintomas Prodrômicos
8.
Sci Rep ; 10(1): 15459, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963331

RESUMO

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A 1H-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA.


Assuntos
Índice de Massa Corporal , Ácidos Graxos/sangue , Metaboloma , Osteoartrite do Quadril/patologia , Osteoartrite do Joelho/patologia , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Osteoartrite do Quadril/sangue , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/epidemiologia , Prevalência , Estudos Prospectivos
9.
Arthritis Rheumatol ; 72(11): 1845-1854, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32840049

RESUMO

OBJECTIVE: To identify robustly differentially expressed long noncoding RNAs (lncRNAs) with osteoarthritis (OA) pathophysiology in cartilage and to explore potential target messenger RNA (mRNA) by establishing coexpression networks, followed by functional validation. METHODS: RNA sequencing was performed on macroscopically lesioned and preserved OA cartilage from patients who underwent joint replacement surgery due to OA (n = 98). Differential expression analysis was performed on lncRNAs that were annotated in GENCODE and Ensembl databases. To identify potential interactions, correlations were calculated between the identified differentially expressed lncRNAs and the previously reported differentially expressed protein-coding genes in the same samples. Modulation of chondrocyte lncRNA expression was achieved using locked nucleic acid GapmeRs. RESULTS: By applying our in-house pipeline, we identified 5,053 lncRNAs that were robustly expressed, of which 191 were significantly differentially expressed (according to false discovery rate) between lesioned and preserved OA cartilage. Upon integrating mRNA sequencing data, we showed that intergenic and antisense differentially expressed lncRNAs demonstrate high, positive correlations with their respective flanking sense genes. To functionally validate this observation, we selected P3H2-AS1, which was down-regulated in primary chondrocytes, resulting in the down-regulation of P3H2 gene expression levels. As such, we can confirm that P3H2-AS1 regulates its sense gene P3H2. CONCLUSION: By applying an improved detection strategy, robustly differentially expressed lncRNAs in OA cartilage were detected. Integration of these lncRNAs with differential mRNA expression levels in the same samples provided insight into their regulatory networks. Our data indicates that intergenic and antisense lncRNAs play an important role in regulating the pathophysiology of OA.


Assuntos
Cartilagem Articular/metabolismo , Epigênese Genética , Osteoartrite do Quadril/metabolismo , Osteoartrite do Joelho/metabolismo , RNA Longo não Codificante/metabolismo , Idoso , Idoso de 80 Anos ou mais , Cartilagem Articular/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/genética , Osteoartrite do Quadril/patologia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/patologia , RNA Longo não Codificante/genética
10.
Aging (Albany NY) ; 12(11): 10129-10146, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32516132

RESUMO

Osteoarthritis (OA) is the most common joint disease characterized by destruction of articular cartilage. OA-induced cartilage degeneration causes inflammation, oxidative stress and the hypertrophic shift of quiescent chondrocytes. Clusterin (CLU) is a ubiquitous glycoprotein implicated in many cellular processes and its upregulation has been recently reported in OA cartilage. However, the specific role of CLU in OA cartilage injury has not been investigated yet. We analyzed CLU expression in human articular cartilage in vivo and in cartilage-derived chondrocytes in vitro. CLU knockdown in OA chondrocytes was also performed and its effect on proliferation, hypertrophic phenotype, apoptosis, inflammation and oxidative stress was investigated. CLU expression was upregulated in human OA cartilage and in cultured OA cartilage-derived chondrocytes compared with control group. CLU knockdown reduced cell proliferation and increased hypertrophic phenotype as well as apoptotic death. CLU-silenced OA chondrocytes showed higher MMP13 and COL10A1 as well as greater TNF-α, Nox4 and ROS levels. Our results indicate a possible cytoprotective role of CLU in OA chondrocytes promoting cell survival by its anti-apoptotic, anti-inflammatory and antioxidant properties and counteracting the hypertrophic phenotypic shift. Further studies are needed to deepen the role of CLU in order to identify a new potential therapeutic target for OA.


Assuntos
Cartilagem Articular/patologia , Clusterina/metabolismo , Osteoartrite do Quadril/patologia , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Cartilagem Articular/citologia , Cartilagem Articular/imunologia , Proliferação de Células/genética , Sobrevivência Celular/genética , Células Cultivadas , Condrócitos , Clusterina/genética , Feminino , Cabeça do Fêmur/patologia , Cabeça do Fêmur/cirurgia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/imunologia , Osteoartrite do Quadril/cirurgia , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia , Cultura Primária de Células , RNA Interferente Pequeno/metabolismo
11.
BMC Musculoskelet Disord ; 21(1): 297, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404085

RESUMO

BACKGROUND: While multiple in vitro studies examined mesenchymal stromal cells (MSCs) derived from bone marrow or hyaline cartilage, there is little to no data about the presence of MSCs in the joint capsule or the ligamentum capitis femoris (LCF) of the hip joint. Therefore, this in vitro study examined the presence and differentiation potential of MSCs isolated from the bone marrow, arthritic hyaline cartilage, the LCF and full-thickness samples of the anterior joint capsule of the hip joint. METHODS: MSCs were isolated and multiplied in adherent monolayer cell cultures. Osteogenesis and adipogenesis were induced in monolayer cell cultures for 21 days using a differentiation medium containing specific growth factors, while chondrogenesis in the presence of TGF-ß1 was performed using pellet-culture for 27 days. Control cultures were maintained for comparison over the same duration of time. The differentiation process was analyzed using histological and immunohistochemical stainings as well as semiquantitative RT-PCR for measuring the mean expression levels of tissue-specific genes. RESULTS: This in vitro research showed that the isolated cells from all four donor tissues grew plastic-adherent and showed similar adipogenic and osteogenic differentiation capacity as proven by the histological detection of lipid droplets or deposits of extracellular calcium and collagen type I. After 27 days of chondrogenesis proteoglycans accumulated in the differentiated MSC-pellets from all donor tissues. Immunohistochemical staining revealed vast amounts of collagen type II in all differentiated MSC-pellets, except for those from the LCF. Interestingly, all differentiated MSCs still showed a clear increase in mean expression of adipogenic, osteogenic and chondrogenic marker genes. In addition, the examination of an exemplary selected donor sample revealed that cells from all four donor tissues were clearly positive for the surface markers CD44, CD73, CD90 and CD105 by flow cytometric analysis. CONCLUSIONS: This study proved the presence of MSC-like cells in all four examined donor tissues of the hip joint. No significant differences were observed during osteogenic or adipogenic differentiation depending on the source of MSCs used. Further research is necessary to fully determine the tripotent differentiation potential of cells isolated from the LCF and capsule tissue of the hip joint.


Assuntos
Adipogenia/genética , Células da Medula Óssea/metabolismo , Cartilagem Hialina/patologia , Cápsula Articular/patologia , Células-Tronco Mesenquimais/metabolismo , Osteoartrite do Quadril/patologia , Ligamento da Cabeça do Fêmur/patologia , Adulto , Antígenos CD/metabolismo , Artroplastia de Quadril , Células Cultivadas , Condrogênese/genética , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Osteoartrite do Quadril/cirurgia , Osteogênese/genética , Doadores de Tecidos
12.
Am J Sports Med ; 48(7): 1647-1656, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32383968

RESUMO

BACKGROUND: Femoroacetabular impingement (FAI) has been proposed as an etiologic factor in up to 50% of hips with osteoarthritis (OA). Inflammation is thought to be one of the main initiators of OA, yet little is known about the origin of intra-articular inflammation in FAI hips. HYPOTHESIS: Articular cartilage from the impingement zone of patients with FAI has high levels of inflammation, reflecting initial inflammatory process in the hip. STUDY DESIGN: Controlled laboratory study. METHODS: Head-neck cartilage samples were obtained from patients with cam FAI (cam FAI, early FAI; n = 15), advanced OA secondary to cam FAI (FAI OA, late FAI; n = 15), and advanced OA secondary to developmental dysplasia of the hip (DDH OA, no impingement; n = 15). Cartilage procured from young adult donors (n = 7) served as control. Safranin O-stained sections were assessed for cartilage abnormality. Tissue viability was detected by TUNEL assay. Immunostaining of interleukin 1ß (IL-1ß), catabolic markers (matrix metalloproteinase 13 [MMP-13], a disintegrin and metalloproteinase with thrombospondin motif 4 [ADAMTS-4], aggrecan antibody to C-terminal neoepitope [NITEGE]), and an anabolic marker (type II collagen [COL2]) was performed to evaluate molecular inflammation and metabolic activity. The average percentage of immunopositive cells from the total cell count was calculated. Kruskal-Wallis test followed by Steel-Dwass post hoc test was used for multiple comparisons. RESULTS: Microscopic osteoarthritic changes were more prevalent in cartilage of cam FAI and FAI OA groups compared with DDH OA and control groups. Cartilage in cam FAI and FAI OA groups, versus the DDH group, had higher expression of inflammatory molecules IL-1ß (69.7% ± 18.1% and 72.5% ± 13.2% vs 32.7% ± 14.4%, respectively), MMP-13 (79.6% ± 12.6% and 71.4% ± 18.8% vs 38. 5% ± 13.3%), ADAMTS-4 (83.9% ± 12.2% and 82.6% ± 12.5% vs 45.7% ± 15.5%), and COL2 (93.6% ± 3.9% and 92.5% ± 5.8% vs 53.3% ± 21.0%) (P < .001). Expression of NITEGE was similar among groups (cam FAI, 89.7% ± 7.7%; FAI OA, 95.7% ± 4.7%; DDH OA, 93.9% ± 5.2%; P = .0742). The control group had minimal expression of inflammatory markers. Inflammatory markers were expressed in all cartilage zones of early and late FAI but only in the superficial zone of the no impingement group. CONCLUSION: Cartilage from the impingement zone in FAI is associated with a high expression of inflammatory markers, extending throughout all cartilage zones. CLINICAL RELEVANCE: Inflammation associated with FAI likely has a deleterious effect on joint homeostasis. Further clinical and translational studies are warranted to assess whether and how surgical treatment of FAI reduces molecular inflammation.


Assuntos
Cartilagem Articular/patologia , Impacto Femoroacetabular/patologia , Osteoartrite do Quadril/etiologia , Biomarcadores/metabolismo , Cartilagem Articular/metabolismo , Feminino , Impacto Femoroacetabular/complicações , Impacto Femoroacetabular/metabolismo , Impacto Femoroacetabular/cirurgia , Humanos , Inflamação/patologia , Interleucina-1beta/metabolismo , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Osteoartrite do Quadril/metabolismo , Osteoartrite do Quadril/patologia
13.
Arthroscopy ; 36(8): 2122-2133, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32259644

RESUMO

PURPOSE: To establish the characteristics of synovium-derived mesenchymal stem cells (MSCs) from the hip joints of patients with femoroacetabular impingement syndrome (FAIS) and osteoarthritis (OA), particularly their proliferation and differentiation potentials. We further investigated their functional differences. METHODS: Synovium samples were harvested from 21 patients with FAIS who underwent hip arthroscopic surgery and from 14 patients with OA who underwent total hip arthroplasty. The MSC number, colony-forming units, cell viability, and differentiation potential were compared. Real-time polymerase chain reaction assessed the differentiation potential into adipose, bone, and cartilage tissues. RESULTS: The number of colonies at a density of 104 at passage 0 from OA synovium was significantly greater than that from FAIS synovium (P < .01). However, their proliferation and viability were significantly lower than those of FAIS synovium cells (P = .0495). The expression of lipoprotein lipase mRNA in OA synovium cells was greater than that in FAIS synovium cells (P < .01). Meanwhile, the fraction of colonies positive for von Kossa and alkaline phosphatase staining, as well as the level of bone gamma-carboxyglutamate protein expression in OA synovium cells, were greater than those in FAIS synovium cells (P < .01). In chondrogenic pellet culture experiments, the expression of COL10A1 mRNA was lower in OA synovium than in FAIS synovium (P < .01). CONCLUSIONS: Synovial MSCs from patients with OA had greater colony numbers but less viability and proliferative potential. They also showed greater osteogenic and adipogenic potentials, whereas those from patients with FAIS showed greater chondrogenic potential. CLINICAL RELEVANCE: MSCs from patients with FAIS exhibited good potential as cell sources for stem cell therapy in case of cartilage damage in the hip joint.


Assuntos
Diferenciação Celular/fisiologia , Impacto Femoroacetabular , Articulação do Quadril , Células-Tronco Mesenquimais/patologia , Osteoartrite do Quadril , Membrana Sinovial/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/fisiologia , Células Cultivadas , Condrogênese/fisiologia , Feminino , Impacto Femoroacetabular/patologia , Impacto Femoroacetabular/fisiopatologia , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/patologia , Articulação do Quadril/fisiopatologia , Articulação do Quadril/cirurgia , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Osteoartrite do Quadril/patologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Quadril/cirurgia , Membrana Sinovial/fisiopatologia , Adulto Jovem
14.
World Neurosurg ; 139: 106-110, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32298829

RESUMO

BACKGROUND: There are few reported cases in the literature of spinal injuries from the past, and all of them resulted in the death of the individual or led to severe health consequences. From the historical record, it is well known there were no cures or treatments for spinal lesions in the past. Given the paucity of historical documents focused on this topic, anthropological research on spinal injuries can contribute with important information regarding the medical history of this kind of trauma. Moreover, skeletal trauma and occupational markers may be crucial for the reconstruction of habitual behaviors and the identification of causes and timing of death. We report results of an anthropological study of a case of vertebral injury discovered in an individual from the Italian Iron Age that highlights this important topic. The aim of this study was to assess the habitual activity pattern and manner of death of an ancient inhabitant of Spina in Padanian Etruria (northeastern Italy). METHODS: We performed a detailed anthropological and paleopathological analysis of skeletal remains. RESULTS: The unknown individual was identified as a middle-aged man characterized by a particular trauma to the spine. Lesion analysis revealed a perimortem injury at the L2-L3 level. Characteristic markers on the bones indicated intense physical activity carried out during his life. CONCLUSIONS: This Etruscan, in all likelihood a sailor according to the occupational markers, did not survive a stabbing attack with a bladed weapon.


Assuntos
Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/patologia , Ferimentos Perfurantes/patologia , Adulto , História Antiga , Humanos , Itália , Vértebras Lombares/patologia , Masculino , Doenças Profissionais/patologia , Osteoartrite do Quadril/patologia , Paleopatologia , Fraturas da Coluna Vertebral/história , Traumatismos da Coluna Vertebral/história , Traumatismos da Coluna Vertebral/patologia , Estresse Fisiológico
15.
Praxis (Bern 1994) ; 109(6): 459-464, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-32345178

RESUMO

From Pathomorphology to Hip Osteoarthritis - Femoroacetabular Impingement as an Example Abstract. Femoroacetabular impingement (FAI) occurs due to abnormal morphology and subsequent contact between the proximal femur and the acetabulum and can be a source of labral and chondral damage in the hip joint. While there is evidence that Cam-type FAI is correlated with hip osteoarthritis, there is yet no clear link between osteoarthritis and Pincer-FAI in which primarily the labrum gets injured. Hips with evident deformity and beginning chondral and/or labral damage should undergo surgery. Most cases (80-90 %) can be successfully treated by hip arthroscopy. At the time of surgery, the typical FAI-patient is 30 years old. With correct indication and proper surgical technique, favorable outcomes are achieved in more than 80 % of the cases at a short- to mid-term follow-up.


Assuntos
Impacto Femoroacetabular , Osteoartrite do Quadril , Acetábulo , Adulto , Artroscopia , Impacto Femoroacetabular/complicações , Impacto Femoroacetabular/patologia , Articulação do Quadril , Humanos , Osteoartrite do Quadril/complicações , Osteoartrite do Quadril/patologia
16.
Sci Rep ; 10(1): 5538, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32218496

RESUMO

Osteoarthritis affects the morphological properties of the femoral head. The goal of this study was to develop a method to elucidate whether these changes are localised to discrete regions, or if the reported trends in microstructural changes may be identified throughout the subchondral bone of the human femoral head. Whole femoral heads extracted from osteoarthritic (n = 5) and healthy controls (n = 5) underwent microCT imaging 39 µm voxel size. The subchondral bone plate was virtually isolated to evaluate the plate thickness and plate porosity. The trabecular bone region was divided into 37 volumes of interest spatially distributed in the femoral head, and bone morphometric properties were determined in each region. The study showed how the developed approach can be used to study the heterogeneous properties of the human femoral head affected by a disease such as osteoarthritis. As example, in the superior femoral head osteoarthritic specimens exhibited a more heterogeneous micro-architecture, with trends towards thicker cortical bone plate, higher trabecular connectivity density, higher trabecular bone density and thicker structures, something that could only be observed with the newly developed approach. Bone cysts were mostly confined to the postero-lateral quadrants extending from the subchondral region into the mid trabecular region. Nevertheless, in order to generalise these findings, a larger sample size should be analysed in the future. This novel method allowed a comprehensive evaluation of the heterogeneous micro-architectural properties of the human femoral head, highlighting effects of OA in the superior subchondral cortical and trabecular bone. Further investigations on different stages of OA would be needed to identify early changes in the bone.


Assuntos
Cistos Ósseos/diagnóstico por imagem , Cabeça do Fêmur/patologia , Osteoartrite do Quadril/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Cistos Ósseos/patologia , Estudos de Casos e Controles , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/patologia , Microtomografia por Raio-X
17.
J Orthop Surg Res ; 15(1): 86, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111250

RESUMO

BACKGROUND: Hip osteoarthritis (HOA) is the most common hip disorder and a major cause of disability in the adult population, with an estimated prevalence of end-stage disease and total hip replacement. Thus, the diagnosis, prevention, and treatment of the early stages of the disease in young adults are crucial to reduce the incidence of end-stage HOA. The purpose of this study was to determine whether (1) a relationship among the inflammatory status of labrum and synovium collected from patients with femoroacetabular impingement (FAI) would exist; and (2) to investigate the associations among the histopathological features of joint tissues, the pre-operative symptoms and the post-operative outcomes after arthroscopic surgery. METHODS: Joint tissues from 21 patients undergoing hip arthroscopy for FAI were collected and their histological and immunohistochemical features were correlated with clinical parameters. RESULTS: Synovial mononuclear cell infiltration was observed in 25% of FAI patients, inversely correlated with the hip disability and osteoarthritis outcome score (HOOS) pain and function subscales and with the absolute and relative change in total HOOS. All the labral samples showed some pattern of degeneration and 67% of the samples showed calcium deposits. The total labral score was associated with increased CD68 positive cells in the synovium. The presence of labral calcifications, along with the chondral damage worsened the HOOS post-op symptoms (adjusted R-square = 0.76 p = 0.0001). CONCLUSIONS: Our study reveals a relationship between the histologic labral features, the synovial inflammation, and the cartilage condition at the time of FAI. The presence of labral calcifications, along with the cartilage damage and the synovitis negatively affects the post-operative outcomes in patients with FAI.


Assuntos
Artralgia/cirurgia , Artroplastia de Quadril/métodos , Calcinose/cirurgia , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/cirurgia , Osteoartrite do Quadril/cirurgia , Adulto , Artralgia/patologia , Artroplastia de Quadril/tendências , Calcinose/patologia , Feminino , Impacto Femoroacetabular/patologia , Articulação do Quadril/patologia , Humanos , Masculino , Osteoartrite do Quadril/patologia
18.
Clin Rheumatol ; 39(7): 2207-2217, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32088798

RESUMO

OBJECTIVES: Recently, several clinical prognostic factors for hip osteoarthritis (OA) progression such as spinal malalignment, reduced spinal mobility, and excessive daily cumulative hip loading have been identified. This study aimed to identify clinical phenotypes based on clinical prognostic factors in patients with secondary hip OA using data from prospective cohort studies and to define the clinical features of each phenotype. METHODS: Fifty patients participated. Two-step cluster analysis was performed to identify the phenotypes using the following potential prognostic factors for hip OA progression: spinal inclination in standing, thoracolumbar spine mobility, daily cumulative hip moment, and minimum joint space width (JSW) at baseline. Comprehensive basic and clinical features (age, body mass index, hip pain, Harris hip score, JSW, radiographic hip morphology, hip impairments, spinal alignment and mobility, and gait-related variables) and ratio of progressors in 12 months were compared among the phenotypes using bootstrap method (unadjusted and adjusted for age). RESULTS: Three phenotypes were identified and each phenotype was characterized as follows (P < 0.05): phenotype 1 (30%)-relatively young age and higher daily cumulative hip loading; phenotype 2 (42.0%)-relatively older age, reduced JSW, and less spinal mobility; and phenotype 3 (28.0%)-changed thoracic spine alignment and less spinal (especially in the thoracic spine) mobility. The ratio of progressors among the phenotypes was not statistically significantly different. These characteristics remained after adjustment for age. CONCLUSION: Three phenotypes with similar progression risk were identified. This finding will help in designing treatment tailored to each phenotype for hip OA progression prevention.Key Points• Three phenotypes with similar progression risk were identified based on clinical prognostic factors.• Phenotype 1 was characterized by young age and higher daily cumulative hip loading.• Phenotype 2 was relatively old age and had reduced JSW and less spinal mobility.• Phenotype 3 had changed thoracic spine alignment and less thoracic spine mobility.


Assuntos
Osteoartrite do Quadril/classificação , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/fisiopatologia , Amplitude de Movimento Articular , Adulto , Progressão da Doença , Feminino , Marcha , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/patologia , Dor/etiologia , Medição da Dor , Fenótipo , Estudos Prospectivos , Radiografia , Fatores de Risco , Vértebras Torácicas/fisiopatologia
19.
Sci Rep ; 10(1): 627, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953438

RESUMO

Subjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (OA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from OA cartilage can be detected in chondrocytes from DDH cartilage before histological manifestations of degeneration. We characterized undamaged and damaged articular cartilage from 22 participants having hip replacement surgery with and without DDH (9 DDH-OA, 12 OA-only, one femoral fracture). Tissue immunostaining revealed changes in damaged OA-only cartilage that was also found in undamaged DDH-OA cartilage. Chondrocytes in situ from both groups show: (i) thicker fibers of vimentin intermediate filaments, (ii) clusters of integrin α5ß1, (iii) positive MMP13 staining and (iv) a higher percentage of cells expressing the serine protease HtrA1. Further characterization of the extracellular matrix showed strong aggrecan and collagen II immunostaining in undamaged DDH cartilage, with no evidence of augmented cell death by activation of caspase 3. These findings suggest that early events in DDH cartilage originate at the chondrocyte level and that DDH cartilage may provide a novel opportunity to study these early changes for the development of therapeutic targets for OA.


Assuntos
Artroplastia de Quadril/métodos , Biomarcadores/metabolismo , Condrócitos/metabolismo , Luxação do Quadril/metabolismo , Osteoartrite do Quadril/metabolismo , Adulto , Idade de Início , Idoso , Agrecanas/metabolismo , Células Cultivadas , Colágeno Tipo II/metabolismo , Feminino , Humanos , Integrina alfa5beta1/metabolismo , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Pessoa de Meia-Idade , Osteoartrite do Quadril/etiologia , Osteoartrite do Quadril/patologia , Vimentina/metabolismo , Adulto Jovem
20.
Osteoarthritis Cartilage ; 28(1): 62-70, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31604136

RESUMO

OBJECTIVE: To design an automated workflow for hip radiographs focused on joint shape and tests its prognostic value for future hip osteoarthritis. DESIGN: We used baseline and 8-year follow-up data from 1,002 participants of the CHECK-study. The primary outcome was definite radiographic hip osteoarthritis (rHOA) (Kellgren-Lawrence grade ≥2 or joint replacement) at 8-year follow-up. We designed a method to automatically segment the hip joint from radiographs. Subsequently, we applied machine learning algorithms (elastic net with automated parameter optimization) to provide the Shape-Score, a single value describing the risk for future rHOA based solely on joint shape. We built and internally validated prediction models using baseline demographics, physical examination, and radiologists scores and tested the added prognostic value of the Shape-Score using Area-Under-the-Curve (AUC). Missing data was imputed by multiple imputation by chained equations. Only hips with pain in the corresponding leg were included. RESULTS: 84% were female, mean age was 56 (±5.1) years, mean BMI 26.3 (±4.2). Of 1,044 hips with pain at baseline and complete follow-up, 143 showed radiographic osteoarthritis and 42 were replaced. 91.5% of the hips had follow-up data available. The Shape-Score was a significant predictor of rHOA (odds ratio per decimal increase 5.21, 95%-CI (3.74-7.24)). The prediction model using demographics, physical examination, and radiologists scores demonstrated an AUC of 0.795, 95%-CI (0.757-0.834). After addition of the Shape-Score the AUC rose to 0.864, 95%-CI (0.833-0.895). CONCLUSIONS: Our Shape-Score, automatically derived from radiographs using a novel machine learning workflow, may strongly improve risk prediction in hip osteoarthritis.


Assuntos
Articulação do Quadril/patologia , Osteoartrite do Quadril/etiologia , Idoso , Algoritmos , Área Sob a Curva , Artrografia , Automação , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/patologia , Prognóstico , Fatores de Risco
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