Osteoarthritis and Cartilage最新文献

{"title":"Sex differences in patellar facet shape among healthy and osteoarthritic cohorts","authors":"","doi":"10.1016/j.joca.2024.06.018","DOIUrl":"10.1016/j.joca.2024.06.018","url":null,"abstract":"<div><h3>Objective</h3><div>Patellofemoral osteoarthritis (OA) may be more common in females than males. Reasons for this are not fully understood, but sex differences in patellar morphology may help explain this phenomenon. We quantified differences in patellar morphology between males and females in healthy and patellofemoral OA populations.</div></div><div><h3>Design</h3><div>A total of 97 (50F, 47M) healthy and 67 (40F, 27M) OA knees were scanned via computed tomography. OA individuals were on a waitlist for total knee replacement. Patella 3D models were segmented and 2D measurements were recorded: patellar width and height, lateral and medial facet width, and surface area. Medial and lateral facet surface topography was mapped using 81 points to describe 3D articular surface shape. Sex and group differences were assessed using Procrustes analysis of variance (ANOVA). Data were ordinated using Principal Component Analysis.</div></div><div><h3>Results</h3><div>Differences in patellar 2D measurements between healthy and OA individuals were smaller than were differences between males and females from healthy and OA groups. Sex and healthy/OA differences were most pronounced for medial facet shape, which featured a posteriorly-curving facet and taller, narrower facet shape in males compared to females. Lateral facet shape variance was higher in OA cohorts compared to healthy groups.</div></div><div><h3>Conclusions</h3><div>Medial and lateral facet shapes showed different patterning of variation by sex and healthy/OA status. Lateral facet shape may be of interest in future models of OA risk in the patellofemoral joint, here showing increased magnitudes of variance associated with increased severity of disease (patellofemoral Kellgren and Lawrence score).</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1433-1442"},"PeriodicalIF":7.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580438","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":"Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study","authors":"","doi":"10.1016/j.joca.2024.06.015","DOIUrl":"10.1016/j.joca.2024.06.015","url":null,"abstract":"<div><h3>Objective</h3><div>To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA).</div></div><div><h3>Design</h3><div>In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates.</div></div><div><h3>Results</h3><div>Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (−1.47 [95%CI −2.88, −0.05]), even while adjusting for synovial inflammation (−1.61 [95%CI −3.12, −0.10]).</div></div><div><h3>Conclusions</h3><div>Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1503-1512"},"PeriodicalIF":7.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545130","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 microRNA and metabolite changes after anterior cruciate ligament reconstruction surgery","authors":"","doi":"10.1016/j.joca.2024.06.013","DOIUrl":"10.1016/j.joca.2024.06.013","url":null,"abstract":"<div><h3>Objectives</h3><p>Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA’s natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males.</p></div><div><h3>Methods</h3><p>A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed.</p></div><div><h3>Results</h3><p>Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log₂-fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log₂-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log₂-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log₂-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males.</p></div><div><h3>Conclusion</h3><p>MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.</p></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 9","pages":"Pages 1113-1125"},"PeriodicalIF":7.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1063458424012664/pdfft?md5=a4e6ccc01b0bc6569d57da1ff8b8e88d&pid=1-s2.0-S1063458424012664-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545131","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":"Immunomodulation and fibroblast dynamics driving nociceptive joint pain within inflammatory synovium: Unravelling mechanisms for therapeutic advancements in osteoarthritis","authors":"","doi":"10.1016/j.joca.2024.06.011","DOIUrl":"10.1016/j.joca.2024.06.011","url":null,"abstract":"<div><h3>Objective</h3><div>Synovitis is a widely accepted sign of osteoarthritis (OA), characterised by tissue hyperplasia, where increased infiltration of immune cells and proliferation of resident fibroblasts adopt a pro-inflammatory phenotype, and increased the production of pro-inflammatory mediators that are capable of sensitising and activating sensory nociceptors, which innervate the joint tissues. As such, it is important to understand the cellular composition of synovium and their involvement in pain sensitisation to better inform the development of effective analgesics.</div></div><div><h3>Methods</h3><div>Studies investigating pain sensitisation in OA with a focus on immune cells and fibroblasts were identified using PubMed, Web of Science and SCOPUS.</div></div><div><h3>Results</h3><div>In this review, we comprehensively assess the evidence that cellular crosstalk between resident immune cells or synovial fibroblasts with joint nociceptors in inflamed OA synovium contributes to peripheral pain sensitisation. Moreover, we explore whether the elucidation of common mechanisms identified in similar joint conditions may inform the development of more effective analgesics specifically targeting OA joint pain.</div></div><div><h3>Conclusion</h3><div>The concept of local environment and cellular crosstalk within the inflammatory synovium as a driver of nociceptive joint pain presents a compelling opportunity for future research and therapeutic advancements.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1358-1370"},"PeriodicalIF":7.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498626","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":"A phase 2b double-blind placebo-controlled randomized clinical trial of SB-061, an aggrecan mimetic, in patients with symptomatic knee osteoarthritis","authors":"","doi":"10.1016/j.joca.2024.06.016","DOIUrl":"10.1016/j.joca.2024.06.016","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the efficacy and safety of intra-articular injections of a novel aggrecan<span> mimetic, SB-061, in subjects with knee osteoarthritis (OA).</span></div></div><div><h3>Methods</h3><div>This was a randomized, placebo-controlled, double-blind phase II study comparing intra-articular injections of SB-061 with placebo (isotonic saline) for 52 weeks, administered at baseline, Wk 16, and Wk 32. Eligible subjects had a KL grade of 2 or 3 on X-ray of the target knee and a Western Ontario McMaster Universities Osteoarthritis<span> Index (WOMAC) pain score ≥20 out of 50 at screening and baseline visits. Subjects having any other knee condition were excluded. Use of analgesics<span><span> was prohibited, except for rescue medication. The primary endpoint was change from baseline (CFB) in </span>WOMAC pain at Week 8. Secondary endpoints were CFB in WOMAC function and total, ICOAP, Patient Global Assessment, and 20-meter walk test. Exploratory endpoints included structural CFB in magnetic resonance imaging entities.</span></span></div></div><div><h3>Results</h3><div>A total of 288 subjects were randomized to SB-061 (n = 145) or placebo (n = 143), and 252 (87.5%) completed injections. The groups were comparable at baseline. The primary endpoint was not met, as no significant difference in the CFB of the WOMAC pain score at Week 8 between groups was observed, nor at any other time point during the study. Similarly, neither of the secondary or exploratory endpoints indicated any significant difference between groups. The frequency and type of adverse events were similar between groups. SB-061 was well-tolerated.</div></div><div><h3>Conclusion</h3><div>Intra-articular injections of SB-061 administered at baseline, Week 16, and Week 32, over one year in subjects with knee OA, were safe but did not show any statistically significant effect on knee pain nor on other symptomatic or structural entities compared to placebo.</div></div><div><h3>Trial registration number EudraCT No</h3><div>2019-004515-31</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1471-1480"},"PeriodicalIF":7.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498625","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":"Anterior cruciate ligament injury and age affect knee cartilage T2 but not thickness","authors":"","doi":"10.1016/j.joca.2024.06.014","DOIUrl":"10.1016/j.joca.2024.06.014","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls.</div></div><div><h3>Design</h3><div>Quantitative double-echo steady-state 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20–30 years: healthy, HEA_20–30, n = 24; ACL-injured, ACL_20–30, n = 23; 40–60 years: healthy, HEA_40–60, n = 24; ACL-injured, ACL_40–60, n = 14 (ACL injury 2–10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side differences in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics.</div></div><div><h3>Results</h3><div>Cartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL_20–30 than in HEA_20–30. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls.</div></div><div><h3>Conclusion</h3><div>In the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in diagnosing and monitoring early articular cartilage changes.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1492-1502"},"PeriodicalIF":7.2,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477155","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":"β2-adrenoceptors kick osteoarthritis – Time to rethink prevention and therapy","authors":"Zsuzsa Jenei-Lanzl ,&nbsp;Rainer H. Straub","doi":"10.1016/j.joca.2024.06.012","DOIUrl":"10.1016/j.joca.2024.06.012","url":null,"abstract":"<div><div>Although, during the past decades, substantial advances emerged in identifying major local and systemic factors contributing to initiation and progression of osteoarthritis (OA), some neuroendocrine mechanisms are still not understood or even neglected when thinking about novel therapeutic options. One of which is the sympathetic nervous system that exhibits various OA-promoting effects in different tissues of the joint. Interestingly, the β2-adrenoceptor (AR) mediates the majority of these effects as demonstrated by several in vitro, in vivo as well as in clinical studies. This review article does not only summarize studies of the past two decades demonstrating that the β2-AR plays an OA-promoting role in different tissues of the joint but also aims to encourage the reader to think about next-level research to discover novel and innovative preventive and/or therapeutic strategies targeting the β2-AR in OA.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 12","pages":"Pages 1522-1529"},"PeriodicalIF":7.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469906","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":"Stem cell injections for knee osteoarthritis: Time for a reality check and some strategic thinking","authors":"","doi":"10.1016/j.joca.2024.06.008","DOIUrl":"10.1016/j.joca.2024.06.008","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 10","pages":"Pages 1179-1180"},"PeriodicalIF":7.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469905","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":"SOARing towards new heights in post-traumatic knee osteoarthritis — New opportunities for prevention","authors":"","doi":"10.1016/j.joca.2024.06.007","DOIUrl":"10.1016/j.joca.2024.06.007","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 8","pages":"Pages 869-871"},"PeriodicalIF":7.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469904","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":"Inverse genetics tracing the differentiation pathway of human chondrocytes","authors":"","doi":"10.1016/j.joca.2024.06.009","DOIUrl":"10.1016/j.joca.2024.06.009","url":null,"abstract":"<div><h3>Objective</h3><div>Mammalian somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) via the forced expression of Yamanaka reprogramming factors. However, only a limited population of the cells that pass through a particular pathway can metamorphose into iPSCs, while the others do not. This study aimed to clarify the pathways that chondrocytes follow during the reprogramming process.</div></div><div><h3>Design</h3><div>The fate of human articular chondrocytes under reprogramming was investigated through a time-coursed single-cell transcriptomic analysis, which we termed an inverse genetic approach. The iPS interference technique was also employed to verify that chondrocytes inversely return to pluripotency following the proper differentiation pathway.</div></div><div><h3>Results</h3><div>We confirmed that human chondrocytes could be converted into cells with an iPSC phenotype. Moreover, it was clarified that a limited population that underwent the silencing of <em>SOX9</em>, a master gene for chondrogenesis, at a specific point during the proper transcriptome transition pathway, could eventually become iPSCs. Interestingly, the other cells, which failed to be reprogrammed, followed a distinct pathway toward cells with a surface zone chondrocyte phenotype. The critical involvement of cellular communication network factors (CCNs) in this process was indicated. The idea that chondrocytes, when reprogrammed into iPSCs, follow the differentiation pathway backward was supported by the successful iPS interference using <em>SOX9</em>.</div></div><div><h3>Conclusions</h3><div>This inverse genetic strategy may be useful for seeking candidates for the master genes for the differentiation of various somatic cells. The utility of CCNs in articular cartilage regeneration is also supported.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1419-1432"},"PeriodicalIF":7.2,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458570","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}