Osteoarthritis and Cartilage最新文献

{"title":"Stress causes lipid droplet accumulation in chondrocytes by impairing microtubules","authors":"Jia Yu ,&nbsp;Qian Liu ,&nbsp;Yuejiao Zhang ,&nbsp;Lingfeng Xu ,&nbsp;Xiaohua Chen ,&nbsp;Feng He ,&nbsp;Mian Zhang ,&nbsp;Hongxu Yang ,&nbsp;Shibin Yu ,&nbsp;Xin Liu ,&nbsp;Yaoping Wu ,&nbsp;Meiqing Wang","doi":"10.1016/j.joca.2024.08.015","DOIUrl":"10.1016/j.joca.2024.08.015","url":null,"abstract":"<div><h3>Objective</h3><div>Abnormal mechanical stress is intimately coupled with osteoarthritis. Microtubules play a vital role in the regulation of mechanotransduction and intracellular transport. The purpose of the present study was to investigate the impact of stress-induced microtubule impairment on intracellular transport and lipid droplet (LD) accumulation in chondrocytes.</div></div><div><h3>Method</h3><div>Rats were subjected to unilateral anterior crossbite (UAC), which is inducible for degeneration of temporomandibular joint (TMJ) cartilage. Chondrocytes derived from rat TMJ cartilage were subjected to fluid flow shear stress (FFSS) and analyzed via LC<img>MS/MS-based proteomics. The microtubule destabilization agent nocodazole and/or the microtubule stabilizer docetaxel were used in the UAC and FFSS models.</div></div><div><h3>Results</h3><div>In both FFSS- and UAC-treated chondrocytes, decreased acetylated α-Tubulin (ac-Tubulin) expression and LD accumulation were observed. Proteomic data revealed increased levels of the LD-associated protein perilipin 3 (Plin3) and decreased levels of cytoskeleton components in FFSS-treated chondrocytes. Live-cell imaging revealed that the colocalization of LDs with lysosomes was significantly decreased after FFSS treatment. Impairment of microtubules by nocodazole reduced the protein level of ac-Tubulin and disrupted the Hsc70-mediated interaction between Plin3 and Lamp2a, as shown by co-IP assays. In contrast, docetaxel reversed the suppression of ac-Tubulin expression, reduced the accumulation of LDs, and decreased the expression of Plin3 in chondrocytes exposed to FFSS and UAC, and docetaxel ameliorated UAC-induced osteoarthritic lesions in the TMJ cartilage.</div></div><div><h3>Conclusion</h3><div>Microtubule impairment under aberrant stress conditions disrupts intracellular transport and blocks lipophagy, causing LD accumulation in chondrocytes. Microtubule stabilization could be a new approach for treating stress-induced cartilage degeneration.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 3","pages":"Pages 351-363"},"PeriodicalIF":7.2,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subchondral bone marrow adipose tissue lipolysis regulates bone formation in hand osteoarthritis","authors":"Mauro Maniglio ,&nbsp;Léa Loisay ,&nbsp;Diego de Haro ,&nbsp;Alexander Antoniadis ,&nbsp;Thomas Hügle ,&nbsp;Jeroen Geurts","doi":"10.1016/j.joca.2024.12.005","DOIUrl":"10.1016/j.joca.2024.12.005","url":null,"abstract":"<div><h3>Objective</h3><div>Bone marrow adipose tissue (BMAT) is emerging as an important regulator of bone formation and energy metabolism. Lipolysis of BMAT releases glycerol and fatty acid substrates that are catabolized by osteoblasts. Here, we investigated whether BMAT lipolysis is involved in subchondral bone formation in hand osteoarthritis (OA).</div></div><div><h3>Methods</h3><div>Subchondral BMAT lipolysis and bone marrow adipocyte (BMAd) morphology were studied in clinical specimens of carpometacarpal (CMC-1) and distal interphalangeal joint OA. BMAd size, osteoblast numbers and expression of lipolysis enzymes (ATGL, phospho-HSL, MGLL) were compared between regions of low and high bone formation. Free fatty acids, glycerol and bone biomarkers were measured in osteochondral explants.</div></div><div><h3>Results</h3><div>Subchondral BMAd size was positively correlated with BMI (<em>r</em> = 0.60, [0.082,0.87]) and reduced in regions of high bone formation (−1149 µm², [−1977,−726.2]). Osteoblast numbers were negatively correlated with BMAd size (<em>r</em> = −0.48, [−0.73,−0.12]). All lipolysis enzymes were expressed in both in BMAds and activated osteoblasts and the area percentages of ATGL (+2.26% [0.19,3.47]), phospho-HSL (+1.57% [0.31,6.48]) and MGLL (+4.04% [1.09,5.69]) were increased in regions of high bone formation. Secreted glycerol levels, but not free fatty acids, were correlated with bone formation markers pro-collagen type I (<em>rho</em> = 0.90) and alkaline phosphatase (<em>rho</em> = 0.78).</div></div><div><h3>Conclusion</h3><div>Our findings reveal a previously unrecognized role of BMAT lipolysis in regulating bone formation in hand OA, which may be modulated by BMI.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 3","pages":"Pages 322-329"},"PeriodicalIF":7.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare variant association studies: Significance, methods, and applications in chronic pain studies","authors":"Sahel Jahangiri Esfahani ,&nbsp;Xiang Ao ,&nbsp;Anahita Oveisi ,&nbsp;Luda Diatchenko","doi":"10.1016/j.joca.2024.12.006","DOIUrl":"10.1016/j.joca.2024.12.006","url":null,"abstract":"<div><div>Rare genetic variants, characterized by their low frequency in a population, have emerged as essential components in the study of complex disease genetics. The biology of rare variants underscores their significance, as they can exert profound effects on phenotypic variation and disease susceptibility. Recent advancements in sequencing technologies have yielded the availability of large-scale sequencing data such as the UK Biobank whole-exome sequencing (WES) cohort empowered researchers to conduct rare variant association studies (RVASs). This review paper discusses the significance of rare variants, available methodologies, and applications. We provide an overview of RVASs, emphasizing their relevance in unraveling the genetic architecture of complex diseases with special focus on chronic pain and Arthritis. Additionally, we discuss the strengths and limitations of various rare variant association testing methods, outlining a typical pipeline for conducting rare variant association. This pipeline encompasses crucial steps such as quality control of WES data, rare variant annotation, and association testing. It serves as a comprehensive guide for researchers in the field of chronic pain diseases interested in rare variant association studies in large-scale sequencing datasets like the UK Biobank WES cohort. Lastly, we discuss how the identified variants can be further investigated through detailed experimental studies in animal models to elucidate their functional impact and underlying mechanisms.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 3","pages":"Pages 313-321"},"PeriodicalIF":7.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic performance of self-reported knee crepitus using a Knee injury and Osteoarthritis Outcome Score item.","authors":"Jamon L Couch, Matthew G King, Danilo De Oliveira Silva, Jackie L Whittaker, Thomas J West, Andrea M Bruder, Michael A Girdwood, Christian J Barton, Kay M Crossley, Ewa M Roos, Adam G Culvenor","doi":"10.1016/j.joca.2024.12.004","DOIUrl":"10.1016/j.joca.2024.12.004","url":null,"abstract":"<p><strong>Objective: </strong>To assess the diagnostic performance of a single Knee injury and Osteoarthritis Outcome Score (KOOS) item in evaluating the presence of knee crepitus.</p><p><strong>Design: </strong>All 184 participants aged 18-40 years with a symptomatic knee, 9-36 months following anterior cruciate ligament reconstruction (ACLR) who were prospectively enrolled in a post-traumatic knee osteoarthritis trial (ACTRN12620001164987) were included. Participants completed the KOOS and underwent physical examination for knee crepitus at baseline. Self-reported knee crepitus (index test) of the ACLR knee was defined as a response of \"often\" or \"always\" on item S2 of the KOOS-Symptom subscale (KOOS-S2: Do you feel grinding, hear clicking or any other type of noise when your knee moves?). The presence of knee crepitus on physical examination (reference standard) was defined as continuous grinding, crunching or crackling during three consecutive squats with the investigator's palm placed lightly over the patella. Sensitivity, specificity, positive (LR+) and negative likelihood ratios (LR-), and positive (PPV) and negative predictive values (NPV), with 95% confidence intervals (CI), were calculated.</p><p><strong>Results: </strong>On physical examination, 113 (62%) participants had knee crepitus, and 71 (39%) met the criteria for self-reported knee crepitus. KOOS-S2 demonstrated a specificity of 73% (95%CI 61%-83%), sensitivity of 47% (95%CI 37%-57%), LR+ of 1.75 (95%CI 1.14-2.70), LR- of 0.72 (95%CI 0.58-0.91), PPV of 74% (95%CI 64%-81%), and NPV of 46% (95%CI 41%-52%).</p><p><strong>Conclusion: </strong>KOOS-S2 may be a useful method to rule in the presence of knee crepitus on physical examination in individuals post-ACLR; however, it is inadequate for ruling out this clinical sign.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetabular dysplasia and the risk of developing hip osteoarthritis within 4-8 years: An individual participant data meta-analysis of 18,807 hips from the World COACH consortium","authors":"Noortje S. Riedstra ,&nbsp;Fleur Boel ,&nbsp;Michiel M.A. van Buuren ,&nbsp;Harbeer Ahedi ,&nbsp;Vahid Arbabi ,&nbsp;Nigel Arden ,&nbsp;Sara J. Baart ,&nbsp;Sita M.A. Bierma-Zeinstra ,&nbsp;Flavia M. Cicuttini ,&nbsp;Timothy F. Cootes ,&nbsp;Kay M. Crossley ,&nbsp;David T. Felson ,&nbsp;Willem Paul Giellis ,&nbsp;Joshua Heerey ,&nbsp;Graeme Jones ,&nbsp;Stefan Kluzek ,&nbsp;Nancy E. Lane ,&nbsp;Claudia Lindner ,&nbsp;John A. Lynch ,&nbsp;Joyce B.J. van Meurs ,&nbsp;Rintje Agricola","doi":"10.1016/j.joca.2024.12.001","DOIUrl":"10.1016/j.joca.2024.12.001","url":null,"abstract":"<div><h3>Objective</h3><div>To study the association between various radiographic definitions of acetabular dysplasia (AD) and incident radiographic hip osteoarthritis (RHOA), and to analyze in subgroups.</div></div><div><h3>Methods</h3><div>Hips free of RHOA at baseline and with follow-up within 4–8 years were drawn from the World COACH consortium. The Wiberg center edge angle (WCEA), acetabular depth width ratio (ADR), and the modified acetabular index (mAI) were calculated. AD was defined as WCEA≤25°, and for secondary analyses as WCEA≤20°, ADR ≤250, mAI ≥ 13°, and a combination. A logistic regression model with generalized mixed effects with 3 levels adjusted for age, biological sex, and body mass index (BMI) was used. Descriptive statistics stratified by age, biological sex and BMI were reported.</div></div><div><h3>Results</h3><div>A total of 18,807 hips from 9 studies were included. Baseline characteristics: age 61.84 (± 8.32) years, BMI 27.40 (± 4.49) kg/m², 70.1% women. 4766 hips (25.3%) had WCEA≤25°. Within 4–8 years (mean 5.8 ±1.6) follow-up, 378 hips (2.0%) developed incident RHOA. We found an association between AD and RHOA (adjusted OR [aOR] 1.80 95% confidence interval [CI] 1.40–2.34). In secondary analyses, all other definitions of AD were also associated with incident RHOA (aOR ranging from 1.52 95% CI 1.19–1.94 to 1.96 95% CI 1.26–3.02). Descriptive statistics showed that the relative risk (RR) in AD hips to develop RHOA was higher compared to non-AD hips in age group 61–70 (RR 1.70), BMI&lt;25 (RR 1.66), and in female hips (RR 1.73).</div></div><div><h3>Conclusion</h3><div>AD was consistently associated with incident RHOA. Explorative analyses show that AD hips in women and age group 61–70 years seem to be more at risk of developing RHOA compared to non-AD hips.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 3","pages":"Pages 373-382"},"PeriodicalIF":7.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor 7 (FGF7) causes cartilage destruction, subchondral bone remodeling, and the premature growth plate closure in mice","authors":"Youngnim Shin,&nbsp;Ji-Sun Kwak,&nbsp;Seul Ki Kim,&nbsp;Jang-Soo Chun","doi":"10.1016/j.joca.2024.11.010","DOIUrl":"10.1016/j.joca.2024.11.010","url":null,"abstract":"<div><h3>Objective</h3><div>Fibroblast growth factor (FGF) signaling plays a significant role in osteoarthritis (OA) pathogenesis, though the OA-related functions of only a few FGFs have been fully elucidated. This study investigates the specific roles of FGF7 in OA development.</div></div><div><h3>Methods</h3><div>FGF7 expression was analyzed in human (n=6) and mouse (n=10) cartilage. Experimental OA was induced by destabilization of the medial meniscus (DMM). The roles of FGF7 were explored using intra-articular (IA) injection of recombinant FGF7 (rFGF7) and whole-body <em>Fgf7</em> knockout mice (<em>Fgf7</em>^<em>-/-</em>). Subchondral bone remodeling and growth plate morphology were assessed micro computed tomography (µCT) and histological analysis.</div></div><div><h3>Results</h3><div>FGF7 was upregulated in OA cartilage. IA injection of rFGF7 led to OA cartilage destruction (OARSI [Osteoarthritis Research Society International] grade; 0.61 [95% CI 0.00–5.33]), while <em>Fgf7</em>^<em>-/-</em> mice showed reduced DMM-induced cartilage erosion (OARSI grade; 1.89 [95% CI 1.08–3.00]) compared to wild-type mice (4.92 [95% CI 3.83–5.33]). These effects were associated with changes in matrix-degrading enzyme expression in chondrocytes. Mice receiving IA injection of rFGF7 (20 μg) exhibited increased subchondral bone thickness (68.01 µm [95% CI 61.55–74.46]) and decreased osteoclastogenesis (tartrate-resistant acid phosphatase positivity; 1.94% [95% CI 1.41–2.47]) compared to controls (38.33 µm [95% CI 33.71–42.96]) and (4.23% [95% CI 3.28–5.19]), respectively. Additionally, rFGF7 treatment caused premature closure of growth plates, whereas <em>Fgf7</em>^<em>-/-</em> mice exhibited significantly increased growth plate thickness.</div></div><div><h3>Conclusions</h3><div>FGF7 exerts multiple functions in various joint tissues, including promoting cartilage destruction, inducing subchondral bone remodeling (SBP thickening), and triggering premature growth plate closure.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 4","pages":"Pages 426-436"},"PeriodicalIF":7.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curculigoside upregulates BMAL1 to decrease nucleus pulposus cell apoptosis by inhibiting the JAK/STAT3 pathway","authors":"Linchuan Lei ,&nbsp;Hua Wang ,&nbsp;Zhuoyang Zhao ,&nbsp;Yuming Huang ,&nbsp;Xiaohui Huang ,&nbsp;Xingyu Guo ,&nbsp;Guowei Jiang ,&nbsp;Shunlun Chen ,&nbsp;Wantao Wang ,&nbsp;Xi Chen ,&nbsp;Zhaomin Zheng ,&nbsp;Jianru Wang ,&nbsp;Fan Chen","doi":"10.1016/j.joca.2024.11.009","DOIUrl":"10.1016/j.joca.2024.11.009","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IVDD) is a natural process that occurs with aging and is the main cause of low back pain. Basic helix-loop-helix ARNT-like 1 (BMAL1) plays key roles in the pathogenesis of many diseases. The present study investigates the role of curculigoside (CUR), which has been reported to be a potential anti-apoptotic compound in other diseases.</div></div><div><h3>Methods</h3><div>Dysregulated genes were identified by RNA sequencing (RNA-seq). Western blotting (WB), immunohistochemistry, immunofluorescence (IF) staining, and real-time fluorescent quantitative polymerase chain reaction were used to detect BMAL1 expression in 25 human intervertebral disc specimens (male: female =13:12), tissues from BMAL1-knockout mice and from an IVDD mouse model. The regulatory effects of CUR and BMAL1 in nucleus pulposus (NP) cells after Small Interfering RNA (siRNA) transfection were examined by flow cytometry, IF staining and WB. The therapeutic effect of intraperitoneal CUR injection was also evaluated in mice.</div></div><div><h3>Results</h3><div>BMAL1 expression was negatively correlated with IVDD severity and was significantly lower in degenerative NP cells. After BMAL1 knockdown using siRNA, the apoptosis rate of degenerative NP cells was significantly higher, while transfection with a lentivirus overexpressing BMAL1 exerted the opposite effect. Bioinformatics analysis revealed that BMAL1 is regulated by the JAK-STAT3 pathway, and CUR upregulated BMAL1 expression by inhibiting STAT3 phosphorylation, subsequently alleviating NP cell apoptosis and increasing extracellular matrix (ECM) components., thus alleviating IVDD.</div></div><div><h3>Conclusions</h3><div>CUR can inhibit apoptosis and improve the ECM by upregulating BMAL1 expression, which is reduced in IVDD. This study provides a therapeutic strategy to alleviate apoptosis associated with inflammation-induced IVDD.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 4","pages":"Pages 412-425"},"PeriodicalIF":7.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-stage vs established knee osteoarthritis: A comparative observational study on prevalence and changes in pain, function and quality of life after supervised exercise and education among 10,365 patients","authors":"S.J.J. Drummen ,&nbsp;J. Runhaar ,&nbsp;S.M. Bierma-Zeinstra ,&nbsp;D. Aitken ,&nbsp;G. Jones ,&nbsp;P. Otahal ,&nbsp;D.T. Grønne ,&nbsp;E.M. Roos ,&nbsp;S.T. Skou","doi":"10.1016/j.joca.2024.11.007","DOIUrl":"10.1016/j.joca.2024.11.007","url":null,"abstract":"<div><h3>Objective</h3><div>Compare prevalence and changes in outcomes among established and early-stage knee osteoarthritis (KOA) patients undertaking supervised exercise and education.</div></div><div><h3>Methods</h3><div>Patients from Good Life with osteoArthritis in Denmark (GLA:D®) were stratified into three groups: established KOA (ACR/EULAR criteria), early-stage KOA (diagnostic-model-outcome ≥70%, Criteria for the Early Diagnosis of knee Osteoarthritis) or potential early-stage KOA (diagnostic-model-outcome 30–69%). Mixed-effects models and the proportion of patients by group achieving minimal clinically important improvements (MCIIs) were used to investigate changes in VAS pain intensity (0–100mm), Knee injury and Osteoarthritis Outcome Score (KOOS) Quality of Life (QoL; 0–100), 40 m Walk test and 30 s chair-stand test at 3 and 12 months.</div></div><div><h3>Results</h3><div>Compared to established KOA (61% of 10,365 patients), early-stage KOA (27%) had similar knee pain at baseline (mean (standard deviation); 51 (22) vs 45 (22)), and improvement in pain (mean (95% confidence interval) −15 (−15 to −14) vs −14 (−15 to −13), ≥MCII: 55% vs 54%) and KOOS QoL (≥MCII: 50% vs 50%) at 12 months, and in walking speed (≥MCII: 56% vs 52%) and chair-stands (≥MCII: 55% vs 52%) at 3 months. Compared to either group, potential early-stage KOA (10%) had lower baseline pain (34 (32.7)) and less improvement in pain (−9.8 (−11.3 to −8.2; ≥MCII: 47%)), but comparable improvements in KOOS QoL (≥MCII: 50%), walking speed (≥MCII: 51%) and chair-stands (≥MCII: 51%).</div></div><div><h3>Conclusion</h3><div>Patients with early-stage KOA achieved comparable improvements at 3 and 12 months to those with established KOA, supporting supervised exercise and education as a viable management strategy for early-stage KOA.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 3","pages":"Pages 364-372"},"PeriodicalIF":7.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA signature for early prediction of knee osteoarthritis structural progression using integrated machine and deep learning approaches","authors":"Afshin Jamshidi ,&nbsp;Osvaldo Espin-Garcia ,&nbsp;Thomas G. Wilson ,&nbsp;Ian Loveless ,&nbsp;Jean-Pierre Pelletier ,&nbsp;Johanne Martel-Pelletier ,&nbsp;Shabana Amanda Ali","doi":"10.1016/j.joca.2024.11.008","DOIUrl":"10.1016/j.joca.2024.11.008","url":null,"abstract":"<div><h3>Objective</h3><div>Conventional methodologies are ineffective in predicting the rapid progression of knee osteoarthritis (OA). MicroRNAs (miRNAs) show promise as biomarkers for patient stratification. We aimed to develop a miRNA prognosis model for identifying knee OA structural progressors/non-progressors using integrated machine/deep learning tools.</div></div><div><h3>Methods</h3><div>Baseline serum miRNAs from Osteoarthritis Initiative (OAI) participants were isolated and sequenced. Participants were categorized based on their likelihood of knee structural progression/non-progression using magnetic resonance imaging and X-ray data. For prediction model development, 152 OAI participants (91 progressors, 61 non-progressors) were used. MiRNA features were reduced through VarClusHi clustering. Key miRNAs and OA determinants (age, sex, body mass index, race) were identified using seven machine learning tools. The final prediction model was developed using advanced machine/deep learning techniques. Model performance was assessed with area under the curve (AUC) (95% confidence intervals) and accuracy. Monte Carlo cross-validation ensured robustness. Model validation used 30 OAI baseline plasma samples from an independent set of participants (14 progressors, 16 non-progressors).</div></div><div><h3>Results</h3><div>Feature clustering selected 107 miRNAs. Elastic Net was chosen for feature selection. An optimized prediction model based on an Artificial Neural Network comprising age and four miRNAs (hsa-miR-556-3p, hsa-miR-3157-5p, hsa-miR-200a-5p, hsa-miR-141-3p) exhibited excellent performance (AUC, 0.94 [0.89, 0.97]; accuracy, 0.84 [0.77, 0.89]). Model validation performance (AUC, 0.81 [0.63, 0.92]; accuracy, 0.83 [0.66, 0.93]) demonstrated the potential for generalization.</div></div><div><h3>Conclusion</h3><div>This study introduces a novel miRNA prognosis model for knee OA patients at risk of structural progression. It requires five baseline features, demonstrates excellent performance, is validated with an independent set, and holds promise for future personalized therapeutic monitoring.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 3","pages":"Pages 330-340"},"PeriodicalIF":7.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specialized pro-resolving mediator Maresin 1 attenuates pain in a mouse model of osteoarthritis","authors":"Yu-Ru V. Shih ,&nbsp;Huchen Tao ,&nbsp;Anna Gilpin ,&nbsp;Yuan-Wen Lee ,&nbsp;Sajeeshkumar Madhurakkat Perikamana ,&nbsp;Shyni Varghese","doi":"10.1016/j.joca.2024.10.018","DOIUrl":"10.1016/j.joca.2024.10.018","url":null,"abstract":"<div><h3>Objective</h3><div>We test whether the specialized pro-resolving molecule Maresin 1 (MaR1) attenuates nociceptive behaviors in mice with osteoarthritis-like pain.</div></div><div><h3>Design</h3><div>Osteoarthritis (OA)-like pain behavior was induced by intra-articular injection of monosodium iodoacetate (MIA) and treated with MaR1 (N=6) or vehicle (N=5) by intraperitoneal injection 8 weeks after injury. Mice without MIA injection were used as control (N=6). Nociceptive behaviors were examined by von Frey and dynamic weight bearing measurements. Calcitonin gene-related peptide (CGRP) expression and activated macrophages in the dorsal root ganglion (DRG) were examined by immunofluorescence staining. The inflammatory profile in circulation was assessed by cytokine array. Calcium imaging was performed to assess the in vitro functional response of DRG neurons from animals with OA-like pain behavior to MaR1 with or without RAR Related Orphan Receptor A (RORA) inverse agonist SR3335.</div></div><div><h3>Results</h3><div>MaR1 attenuated knee pain behavior in treated mice (N=6) compared to non-treated mice (N=5) as shown by increased paw withdrawal threshold with a mean difference of 112.2% (95% CI [49.79, 174.6], p=0.0784) at 4 h and 150.9% (95% CI [104.2, 197.5], p=0.0001) at 4 days post-MaR1 treatment, and increased weight bearing with a mean difference of 20.08% (95% CI [2.798, 37.37], p=0.0277) at 1 day post-MaR1 treatment. CGRP expression and activated macrophages were decreased in the DRG, and inflammatory cytokine levels in the circulation were attenuated. Calcium imaging showed MaR1 reduced the functional response of DRG neurons through RORA.</div></div><div><h3>Conclusions</h3><div>Our results show that MaR1 reduces OA-like pain behavior in mice and could be a potential treatment for OA pain.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 3","pages":"Pages 341-350"},"PeriodicalIF":7.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}