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The Journal of Rheumatology Sep 2023To evaluate knee osteoarthritis (KOA) and multijoint osteoarthritis (MJOA), and to compare features by sex and race and ethnicity in a population-based cohort.
OBJECTIVE
To evaluate knee osteoarthritis (KOA) and multijoint osteoarthritis (MJOA), and to compare features by sex and race and ethnicity in a population-based cohort.
METHODS
Participants (n = 544) enrolled in the Johnston County Health Study (JoCoHS) as of January 2023 were categorized by radiographic and symptomatic KOA and MJOA phenotypes, and frequencies were compared by sex and race and ethnicity. Symptoms were assessed according to the Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain, aching, and stiffness (PAS) scores at various joints. Models produced estimates (odds ratio [OR] or mean ratios [MR] and 95% CI) adjusted for age, BMI (kg/m), and education.
RESULTS
Men had twice the odds of having MJOA-6 (≥ 3 lower extremity joints affected); there were no significant differences in MJOA phenotypes by race and ethnicity. Women had 50% higher odds of having KOA or having various features of KOA. Women reported significantly worse KOOS Symptoms scores (MR 1.25). Black participants had higher odds of more severe KOA (OR 1.47), subchondral sclerosis (OR 2.06), and medial tibial osteophytes (OR 1.50). Black participants reported worse KOOS Symptoms than White participants (MR 1.18). Although not statistically significant, Hispanic participants (vs non-Hispanic participants) appeared to have lower odds of radiographic changes but reported worse symptoms.
CONCLUSION
Preliminary findings in the diverse JoCoHS cohort suggest more lower extremity- predominant MJOA in men compared to women. Women and Black participants had more KOA features and more severe symptoms. Hispanic participants appear to have higher pain and symptoms scores despite having fewer structural changes. Studies in diverse populations are needed to understand the burden of OA.
PubMed: 37714542
DOI: 10.3899/jrheum.2023-0479 -
Arthritis Research & Therapy Jan 2024Variations in bone morphology in patients with hip osteoarthritis (HOA) can be broadly categorized into three types: atrophic, normotrophic, and hypertrophic. Despite...
BACKGROUND
Variations in bone morphology in patients with hip osteoarthritis (HOA) can be broadly categorized into three types: atrophic, normotrophic, and hypertrophic. Despite the investigations examining clinical elements, such as bone morphology, pain, and range of motion, our understanding of the pathogenesis of HOA remains limited. Previous studies have suggested that osteophytes typically originate at the interface of the joint cartilage, periosteum, and synovium, potentially implicating synovial mesenchymal stem cells (SMSCs) in the process. This study aimed to investigate the potential factors that drive the development of bone morphological features in HOA by investigating the characteristics of the synovium, differentiation potential of SMSCs, and composition of synovial fluid in different types of HOA.
METHODS
Synovial tissue and fluid were collected from 30 patients who underwent total hip arthroplasty (THA) with the variable bone morphology of HOA patients. RNA sequencing analysis and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were performed to analyse the genes in the normotrophic and hypertrophic synovial tissue. SMSCs were isolated and cultured from the normotrophic and hypertrophic synovial tissues of each hip joint in accordance with the variable bone morphology of HOA patients. Cell differentiation potential was compared using differentiation and colony-forming unit assays. Cytokine array was performed to analyse the protein expression in the synovial fluid.
RESULTS
In the RNA sequencing analysis, 103 differentially expressed genes (DEGs) were identified, predominantly related to the interleukin 17 (IL-17) signalling pathway. Using a protein-protein interaction (PPI) network, 20 hub genes were identified, including MYC, CXCL8, ATF3, NR4A1, ZC3H12A, NR4A2, FOSB, and FOSL1. Among these hub genes, four belonged to the AP-1 family. There were no significant differences in the tri-lineage differentiation potential and colony-forming capacity of SMSCs. However, RT-qPCR revealed elevated SOX9 expression levels in synovial tissues from the hypertrophic group. The cytokine array demonstrated significantly higher levels of CXCL8, MMP9, and VEGF in the synovial fluid of the hypertrophic group than in the normotrophic group, with CXCL8 and MMP9 being significantly expressed in the hypertrophic synovium.
CONCLUSION
Upregulation of AP-1 family genes in the synovium and increased concentrations of CXCL8, MMP9, and VEGF were detected in the synovial fluid of the hypertrophic group of HOA patients, potentially stimulating the differentiation of SMSCs towards the cartilage and thereby contributing to severe osteophyte formation.
Topics: Humans; Matrix Metalloproteinase 9; Osteoarthritis, Hip; Transcription Factor AP-1; Vascular Endothelial Growth Factor A; Mesenchymal Stem Cells; Cytokines
PubMed: 38200556
DOI: 10.1186/s13075-023-03252-y -
Osteoarthritis and Cartilage Mar 2024The crosstalk of joint pathology with local lymph nodes in osteoarthritis (OA) is poorly understood. We characterized the change in T cells in lymph nodes following...
OBJECTIVE
The crosstalk of joint pathology with local lymph nodes in osteoarthritis (OA) is poorly understood. We characterized the change in T cells in lymph nodes following load-induced OA and established the association of the presence and migration of T cells to the onset and progression of OA.
METHODS
We used an in vivo model of OA to induce mechanical load-induced joint damage. After cyclic tibial compression of mice, we analyzed lymph nodes for T cells using flow cytometry and joint pathology using histology and microcomputed tomography. The role of T-cell migration and the presence of T-cell type was examined using T-cell receptor (TCR)α-/- mice and an immunomodulatory drug, Sphingosine-1-phosphate (S1P) receptor inhibitor-treated mice, respectively.
RESULTS
We demonstrated a significant increase in T-cell populations in local lymph nodes in response to joint injury in 10, 16, and 26-week-old mice, and as a function of load duration, 1, 2, and 6 weeks. T-cell expression of inflammatory cytokine markers increased in the local lymph nodes and was associated with load-induced OA progression in the mouse knee. Joint loading in TCRα-/- mice reduced both cartilage degeneration (Osteoarthritis Research Society International (OARSI) scores: TCRα 0.568, 0.981-0.329 confidence interval (CI); wild type (WT) 1.328, 2.353-0.749 CI) and osteophyte formation. Inhibition of T-cell egress from lymph nodes attenuated load-induced cartilage degradation (OARSI scores: Fingolimod: 0.509, 1.821-0.142 CI; Saline 1.210, 1.932-0.758 CI) and decreased localization of T cells in the synovium.
CONCLUSIONS
These results establish the association of lymph node-resident T cells in joint damage and suggest that the S1P receptor modulators and T-cell immunotherapies could be used to treat OA.
Topics: Animals; Mice; X-Ray Microtomography; T-Lymphocytes; Osteoarthritis; Cartilage; Knee Joint; Disease Models, Animal; Cartilage, Articular
PubMed: 38072172
DOI: 10.1016/j.joca.2023.11.021 -
The Spine Journal : Official Journal of... Aug 2023The annular epiphysis (AE) is a peripheral ring of cortical bone that forms a secondary ossification center in the superior and inferior surfaces of vertebral bodies...
BACKGROUND CONTEXT
The annular epiphysis (AE) is a peripheral ring of cortical bone that forms a secondary ossification center in the superior and inferior surfaces of vertebral bodies (VBs). The AE is the last ossification site in the skeleton, typically forming at about the 25th year of life. The AE functions jointly with vertebral endplates to anchor the intervertebral discs to the VBs.
PURPOSE
To establish accurate data on the sizes of the AE of the cervical spine (C3-C7); to compare the ratios between areas and the ratios of the AE to VBs; to compare the ratios between the superior and inferior VB surface areas; and to compare AE lengths between the posterior and anterior midsagittal areas.
STUDY DESIGN
Measurement of 424 cervical spines (C3-C7) obtained from the skeletal collection of the Natural History Museum, Cleveland, Ohio (USA).
METHODS
The sample was characterized by sex, age, and ethnic origin. The following measurements were recorded for each vertebra: (1) the surface area of the VBs and the AE, (2) the midsagittal anterior and posterior length of the AE, (3) the ratios between the AE and VB surface areas, and (4) the ratios between the superior and inferior disc surface areas.
RESULTS
The study revealed that the AE and VBs in men were larger than in women. With age, the AE and VBs became larger; the ratio between the AE and VB surface was approximately 0.5 throughout the middle to lower cervical spine. The ratio of superior to inferior VBs was approximately 0.8. We found no differences between African Americans versus European Americans or between the anterior versus the posterior midsagittal length of the AE of the superior and inferior VBs.
CONCLUSIONS
The ratios between the superior and inferior VBs are ≥0.8, and the ratio is the same for the entire middle to lower spine. Thus, the ratio between the superior and inferior VBs to the AE is ≥ 0.5. Men had larger AEs and VBs than women did, with both VBs and AEs becoming larger with age. Knowing these relationships are important so that orthopedic surgeons can best correct these issues in young patients (<25 years old) during spine surgery. The data reported here provide, for the first time, all the relevant sizes of the AE and VB. In future studies, AEs and VBs of living patients can be measured with computed tomography.
CLINICAL SIGNIFICANCE
The ER location and function are clinically significant showing any changes during life that might lead to clinical issues related to intervertebral discs such as intervertebral disc asymmetry, disc herniation, nerve pressure, cervical osteophytes and neck pain.
Topics: Male; Humans; Female; Adult; Cervical Vertebrae; Neck; Intervertebral Disc; Tomography, X-Ray Computed; Epiphyses
PubMed: 37141994
DOI: 10.1016/j.spinee.2023.04.006 -
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2024Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex-linked gut microbiome in the pathogenesis of OA.
OBJECTIVE
Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex-linked gut microbiome in the pathogenesis of OA.
METHODS
We induced OA via destabilization of the medial meniscus surgery in adult male and female C57BL6/J mice with and without opposite-sex microbiome transplantation. Eight weeks later, animals were euthanized, and OA severity, synovitis, and osteophyte scores were determined. Serum lipopolysaccharide was measured chromogenically, and serum cytokines were quantified via multiplex immunoassay. Cecal microbiome profiles were generated using 16S deep sequencing.
RESULTS
Males had worse OA histology (3.5x, P = 6 × 10 ), synovitis (2.4x, P = 5 × 10 ), and osteophyte scores (3.7x, P = 3 × 10 ) than females. Male-into-female transplantation worsened all outcomes (histology 1.8x, P = 0.02; synovitis 2.0x, P = 3 × 10 ; osteophyte 2.1x, P = 0.01) compared to females, whereas female-into-male transplantation improved all outcomes except for synovitis (histology 0.53x, P = 2 × 10 ; osteophyte 0.28x, P = 5 × 10 ) compared to males. In the gut microbiome analysis, 44 clades were different in at least one group comparison; 5 clades were correlated with the Osteoarthritis Research Society International score (Lactobacillus R = -0.40, Aldercreutzia R = -0.40, rc4_4 R = -0.55, Sutterella R = -0.37, and Clostridiales R = 0.36). In the cytokine analysis, 10 analytes were different in at least one group comparison; 3 were different in two groups (female and female-into-male transplants vs male comparisons, all reduced in female and female-into-male transplants), including interleukin-12 (0.66x, P = 0.02; 0.66x, P = 0.02, respectively), eotaxin (0.74x, P = 5 × 10 ; 0.57x, P = 0.03), and tumor necrosis factor ⍺ (0.49x, P = 0.03; 0.52x, P = 0.009).
CONCLUSION
Sex-linked differences in the mouse gut microbiome are associated with OA outcomes, are reversible by opposite-sex microbiome transplantation, and are associated with serum cytokine changes.
Topics: Male; Female; Mice; Animals; Gastrointestinal Microbiome; Osteophyte; Osteoarthritis; Mice, Inbred C57BL; Synovitis; Cytokines; Cartilage, Articular
PubMed: 37651283
DOI: 10.1002/art.42687 -
PloS One 2023To gain better understanding of osteoarthritis (OA) heterogeneity and its predictors for distinguishing OA phenotypes. This could provide the opportunity to tailor...
OBJECTIVE
To gain better understanding of osteoarthritis (OA) heterogeneity and its predictors for distinguishing OA phenotypes. This could provide the opportunity to tailor prevention and treatment strategies and thus improve care.
DESIGN
Ten year follow-up data from CHECK (1002 early-OA subjects with first general practitioner visit for complaints ≤6 months before inclusion) was used. Data were collected on WOMAC (pain, function, stiffness), quantitative radiographic tibiofemoral (TF) OA characteristics, and semi-quantitative radiographic patellofemoral (PF) OA characteristics. Using functional data analysis, distinctive sets of trajectories were identified for WOMAC, TF and PF characteristics, based on model fit and clinical interpretation. The probabilities of knee membership to each trajectory were used in hierarchical cluster analyses to derive knee OA phenotypes. The number and composition of potential phenotypes was selected again based on model fit (silhouette score) and clinical interpretation.
RESULTS
Five trajectories representing different constant levels or changing WOMAC scores were identified. For TF and PF OA, eight and six trajectories respectively were identified based on (changes in) joint space narrowing, osteophytes and sclerosis. Combining the probabilities of knees belonging to these different trajectories resulted in six clusters ('phenotypes') of knees with different degrees of functional (WOMAC) and radiographic (PF) parameters; TF parameters were found not to significantly contribute to clustering. Including baseline characteristics as well resulted in eight clusters of knees, dominated by sex, menopausal status and WOMAC scores, with only limited contribution of PF features.
CONCLUSIONS
Several stable and progressive trajectories of OA symptoms and radiographic features were identified, resulting in phenotypes with relatively independent symptomatic and radiographic features. Sex and menopausal status may be especially important when phenotyping knee OA patients, while radiographic features contributed less. Possible phenotypes were identified that, after validation, could aid personalized treatments and patients selection.
Topics: Humans; Osteoarthritis, Knee; Disease Progression; Radiography; Knee Joint; Phenotype
PubMed: 37450467
DOI: 10.1371/journal.pone.0283717 -
Medicine Sep 2023To explore the relationship between knee osteophytes of osteoarthritic knee and calcitonin gene-related peptide (CGRP) concentrations of serum and synovial fluid (SF)....
To explore the relationship between knee osteophytes of osteoarthritic knee and calcitonin gene-related peptide (CGRP) concentrations of serum and synovial fluid (SF). 65 patients with knee medial compartment osteoarthritis (OA) were recruited and examined with weight-bearing radiographs of the entire lower limb. The concentrations of CGRP in serum/SF were also detected in surgery. The relationship between the concentrations of CGRP in serum/SF and osteophyte scores were detected with Spearman rank correlation coefficient. CGRP concentrations in serum and SF were significantly correlated with osteophyte score of overall knee respectively (R = 0.462, P < .001; R = 0.435, P < .001). In addition, a correlation tended to be observed about the relationship between CGRP concentrations in serum and SF and osteophyte scores of medial compartment (R = 0.426, P < .001; R = 0.363, P = .003), and osteophyte scores of lateral compartment (R = 0.429, P < .001; R = 0.444, P < .001). In this study, the relationship between CGRP in serum/SF and knee osteophyte scores in different subregions were explored, which showed significant positive correlations, that possibly reflecting the contribution of CGRP influencing osteophyte formation. Positive correlations between osteophyte scores and CGRP suggest that CGRP promote the growth of osteophyte formation. It has the potential to be selected as a biomarker for the assessment of severity in knee OA patients and predict the progression of knee OA. It also provides a potential therapeutic target to delay the progression and relieve the symptom of OA.
Topics: Humans; Calcitonin Gene-Related Peptide; Osteophyte; Synovial Fluid; Lower Extremity; Osteoarthritis, Knee
PubMed: 37657066
DOI: 10.1097/MD.0000000000034691 -
Cureus Oct 2023This systematic review aims to assess the contemporary literature on the incidence rate, functional scores, and clinical outcomes of heterotopic ossification (HO)... (Review)
Review
This systematic review aims to assess the contemporary literature on the incidence rate, functional scores, and clinical outcomes of heterotopic ossification (HO) following shoulder arthroplasty. We conducted a thorough literature search on EMBASE, MEDLINE, and Ortho Search to identify studies that directly compared patients with and without HO following hemiarthroplasty, anatomic total shoulder arthroplasty (aTSA), or reverse total shoulder arthroplasty (rTSA). We included studies with a minimum follow-up period of one year published from January 2000 to March 2023. We excluded case reports, editorials, and reviews. We performed the systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of the 297 studies initially identified, seven met our inclusion criteria. These studies evaluated a total of 1,134 arthroplasties (212 hemiarthroplasties, 376 aTSAs, and 546 rTSAs). The mean follow-up period was 30.52 (12-120) months and the mean age was 68.69 (20-92). The overall incidence rate of HO was 26.8% (304/1,134). Male gender was associated with a higher incidence rate of HO in three studies. No statistically significant difference was noted in symptoms at follow-up or in Constant-Murley score at two years of follow-up (HO vs. non-HO: 70 vs. 75, p = 0.081). Only one study reported a significant difference in the post-arthroplasty range of motion, specifically in forward elevation (121° vs. 133°, p = 0.0087) and external rotation (19° vs. 25°, p-value = 0.0266). We conclude that HO after shoulder arthroplasty does not display a significant impact on postoperative symptoms or functional outcomes in the majority of patients. To fully comprehend its effect, further research and consensus among experts is necessary.
PubMed: 38021631
DOI: 10.7759/cureus.47374 -
Molecular Medicine Reports Nov 2023Osteoarthritis (OA) is a degenerative disease that ultimately leads to joint deformity. The pathogenesis of OA is believed to involve abnormal chondrocyte death, with...
Osteoarthritis (OA) is a degenerative disease that ultimately leads to joint deformity. The pathogenesis of OA is believed to involve abnormal chondrocyte death, with ferroptosis serving a key role in chondrocyte damage. The present study investigated whether acetyl zingerone (AZ), a newly identified antioxidant derived from curcumin, can alleviate the progression of OA. To investigate this, the present study performed various experiments, including crystal violet staining, flow cytometry, immunofluorescence and western blot analysis. In addition, dual validation was performed using and experiments; a mouse OA model was constructed for the experiments, and chondrocytes were used for the experiments. Destabilization of the medial meniscus (DMM) surgery was performed to establish an OA model in mice and IL‑1β was used to induce an OA model . The results indicated that AZ may promote chondrocyte viability and the expression of extracellular matrix components. Furthermore, AZ reduced the occurrence of ferroptosis by promoting the expression of glutathione peroxidase 4, inhibiting cartilage destruction and osteophyte formation, and alleviating damage to articular cartilage caused by DMM surgery. Mechanistically, the activation of nuclear factor erythroid 2‑related factor 2 and heme oxygenase‑1 may be responsible for the anti‑ferroptosis effects of AZ on chondrocytes. These findings indicated that AZ may be considered a promising candidate for OA therapy.
Topics: Animals; Mice; Chondrocytes; Apoptosis; Ferroptosis; Guaiacol; Disease Models, Animal
PubMed: 37711057
DOI: 10.3892/mmr.2023.13089 -
Clinical Orthopaedics and Related... Nov 2023The distribution of subchondral bone density in a joint represents stress that is applied to the joint. Knowing this information is important for understanding the...
BACKGROUND
The distribution of subchondral bone density in a joint represents stress that is applied to the joint. Knowing this information is important for understanding the pathophysiology of osteoarthritis (OA). In the elbow, however, this has not been studied before.
QUESTIONS/PURPOSES
(1) Is advanced-stage elbow OA associated with more radially distributed subchondral bone density than earlier stages? (2) What demographic (age and sex) and radiographic (osteophyte location and carrying angle) factors are associated with increased radial shift in subchondral bone density?
METHODS
Between March 2001 and December 2021, we treated 301 patients for elbow OA. We considered patients with plain radiographs and conventional CT scans as potentially eligible. Thus, 68% (206 patients) were eligible; a further 27% (80 patients) were excluded because of a history of any injury or surgery or known inflammatory joint disease, leaving 42% (126 patients) for analysis here. Their mean ± standard deviation age was 60 ± 10 years. Early OA with minimal joint space narrowing and osteophyte formation was found in 33% (42 of 126) of patients, and advanced OA was found in the remaining 67% (84 of 126). Three-dimensional distal humerus subchondral bone models were derived from CT images, and in the central intra-articulating portion, we measured the subchondral bone density in two different sites: where it articulates with the radius (SBDrad) and with the ulna (SBDulna). We further defined the SBDratio as the percent ratio of SBDrad to SBDulna. We also evaluated osteophyte severity based on its size at the radiocapitellar and ulnotrochlear joints, and alignment through measuring the carrying angle on radiographs. To assess interobserver reliability, two orthopaedic surgeons took measurements independently from each other. All measurements had excellent intraoberver and interobserver reliabilities. Then, we compared the subchondral bone parameters between early and advanced OA and performed a multivariable analysis of the factors associated with subchondral bone parameters, including age, sex, osteophyte location, and carrying angle.
RESULTS
Radial versus ulna subchondral bone density (SBDratio) was modestly higher in patients with advanced OA (118% ± 17%) than in patients with early OA (109% ± 17%, mean difference 9% [95% CI 2.3% to 15.3%]; p = 0.01). With increasing radial deviation in subchondral bone density, cubitus valgus had a modest association (β = 0.46 ± 0.23; p = 0.04) and severe osteophytes at the radiocapitellar joint had a large association (β = 9.51 ± 3.06; p = 0.002).
CONCLUSION
According to subchondral bone density distribution, stress concentration was more radially deviated in patients with the advanced stages of elbow OA than in those with the early stages. We also found that an increase in carrying angle is associated with radial deviation of stress. A future study that examines longitudinal changes in the subchondral bone density might be required to confirm changes in stress concentration with OA progression.
CLINICAL RELEVANCE
This study gives us insight into the potential pathophysiology of elbow OA in relation to elbow alignment. Although debridement of osteophytes in the ulnotrochlear joint is the most frequently performed procedure in patients with advanced elbow OA, our finding suggests that some patients with an increased carrying angle might benefit from management of the radiocapitellar joint as well, or from being informed of the future development of OA in the radiocapitellar joint, because stress at this site can be increased with the advancement of OA.
PubMed: 37966302
DOI: 10.1097/CORR.0000000000002921