Osteoarthritis and Cartilage最新文献

Objective: The pivotal role of mitophagy in the initiation and progression of intervertebral disc (IVD) degeneration (IDD) has become increasingly apparent due to a growing body of research on its pathogenesis. This review summarizes the role of mitophagy in IDD and the therapeutic potential of targeting this process.

Design: This narrative review is divided into three parts: the regulatory mechanisms of mitophagy, the role of mitophagy in IDD, and the applications and prospects of mitophagy for the treatment of IDD.

Results: Mitophagy protects cells against harmful external stimuli and plays a crucial protective role by promoting extracellular matrix (ECM) production, inhibiting ECM degradation, and reducing apoptosis, senescence, and cartilage endplate calcification. However, excessive mitophagy is often detrimental to cells. Currently, the regulatory mechanisms governing appropriate and excessive mitophagy remain unclear.

Conclusions: Proper mitophagy effectively maintains IVD cell homeostasis and slows the progression of IDD. Conversely, excessive mitophagy may accelerate IDD development. Further research is needed to elucidate the regulatory mechanisms underlying appropriate and excessive mitophagy, which could provide new theoretical support for the application of mitophagy targeting to the treatment of IDD.

Objective: The purpose of this narrative review is to highlight the advances made in the past 12 months in the field of osteoarthritis genetics, genomics and epigenetics.

Methods: The Medline and Embase databases were systematically searched for original publications using terminology, and combinations of terminology, relating to: "osteoarthritis", "genetics", "genomics", and "epigenetics". Only original research articles published in the English language between the OARSI congresses of April 2032 and April 2024 were considered.

Results: This narrative review focuses only on studies using genome-wide omics techniques in human material. There was a rise in functional genomics studies across different osteoarthritis-relevant tissues, which have robustly identified an additional 26 genes involved in osteoarthritis pathology. Two of such previously identified genes (MGP, ALDH1A2) are currently the target of ongoing clinical trials for osteoarthritis. This past year also saw the use of single-cell transcriptomics and two relatively new omics: epitranscriptomics and mitochondrial genomics.

Conclusion: This past year of genomics research has led to multiple exciting findings involving genes and mechanisms linked to osteoarthritis. Moreover, the comprehensive genome-wide omics datasets generated for diverse osteoarthritis tissues will prove invaluable for future research aimed at elucidating more causal biological mechanisms and possible therapeutic targets for osteoarthritis.

Objectives: Previous genetic and animal studies indicated a causal role of thyroid hormones in osteoarthritis (OA), which has not been observed in the general population. We aimed to investigate whether thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were associated with hand, hip, or knee OA.

Methods: Participants from the Rotterdam Study with baseline TSH, FT4, and joint radiographs were included. We used multivariable regression models to investigate the association of thyroid function with the prevalence, severity, incidence, and progression of OA. We conducted stratified analyses by sex, age, body mass index (BMI) and weight-bearing physical activity.

Results: Among 9054 participants included (mean age 65 years, 56.3% women), higher FT4 concentrations were associated with an increased risk of prevalent knee OA (odd ratio [OR] 1.04 per pmol/L, 95% CI 1.01-1.06, corresponding to an OR of 1.62 across the reference range [i.e., 14pmol/L changes] of FT4) and more severe knee OA. There was a positive association between FT4 and overall progression of knee OA (OR 1.03 per pmol/L, 1.00-1.07). No association of TSH with hand, hip, or knee OA was identified. Stratified analysis revealed an association between FT4 and prevalent knee OA among individuals with BMI ≥30 kg/m² (OR 1.05 per pmol/L, 1.01-1.08) and those with high levels of weight-bearing physical activity (OR 1.05 per pmol/L, 1.01-1.10).

Conclusions: Our study indicated that higher FT4 concentrations may increase the risk of knee OA. This association might be greater in individuals with extra joint loading, such as those with obesity.

Objective: To assess the longitudinal stability of biomarker-based molecular endotypes of knee osteoarthritis (KOA) participants from APPROACH and to evaluate the consistency of findings in an independent KOA population.

Methods: Nineteen biomarkers were measured longitudinally in 295 KOA participants from the APPROACH cohort. K-means clustering was used to identify the structural damage, inflammation, and low tissue turnover endotypes at the six-, 12-, and 24-month follow-ups. Endotype stability was defined as having the same independent endotype assignment longitudinally for patients with complete data (n = 226). Clinical and biochemical characteristics were compared between participants with longitudinally stable and unstable endotypes. The presence and longitudinal stability of the endotypes were evaluated in a different KOA population from the placebo arm of the oral salmon calcitonin trials.

Results: An average overall longitudinal endotype stability of 55% (Fleiss' Kappa of 0.53; 95% confidence interval [CI]: 0.46, 0.60) was demonstrated. An average stability of 59% (range: 54-59%) was observed for the structural damage endotype (Fleiss' Kappa 0.52; 95% CI: 0.45, 0.60), 54% (52-56%) for the inflammatory (Fleiss' Kappa 0.61; 95% CI: 0.53, 0.68), and 50% (49-52%) for the low tissue turnover endotype (Fleiss' Kappa 0.46; 95% CI: 0.39, 0.54). Participants with longitudinally unstable endotypes exhibited molecular properties of more than one endotype, which were detectable already at the first visit.

Conclusions: Our study showed for the first time that more than half of KOA participants exhibited a longitudinally stable endotype, highlighting the applicability of biomarker-based endotyping in a clinical trial setting.

Objective: To generate a list of candidate items potentially useful for discriminating individuals with Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) from those with other conditions and from established osteoarthritis (OA), and to reduce this list based on expert consensus.

Design: We conducted a three-round online international modified Delphi exercise with OA clinicians and researchers ("OA experts"). In Round 1, participants reviewed 84 candidate items and nominated additional item(s) potentially useful for EsSKOA classification; those nominated by ≥3 participants were added. In Round 2, participants rated perceived usefulness of 108 items (1 [not at all useful] to 9 [extremely useful]). In Round 3, participants could revise their ratings after reviewing Round 2 group median and quartiles. Following Round 3, we retained items with a median usefulness score >5 and ≥33.3% of participants categorised the item as useful (7 to 9), overall and in subgroup analysis by clinician field.

Results: There were 128 participants in Round 1 and 113 (88%) completed all rounds. We retained 77 items that spanned multiple domains (demographics, symptoms, physical exam, performance-based measures, imaging, laboratory investigations, and gross inspection/arthroscopy). Highly rated items included (median usefulness score): prior knee joint injury (8), diagnosis of OA in a different joint (7), and activity-related knee pain (7). The interquartile range was most often 3.

Conclusion: We identified 77 items that OA experts consider potentially useful for EsSKOA classification. The results highlight experts' uncertainty around item usefulness. Next, candidate items will be further assessed and reduced using data-driven and multicriteria decision analysis methods.

Objective: Anterior cruciate ligament (ACL) injuries are a major problem in the pediatric and adolescent populations. Some of these injuries are only partial; yet, there is limited data to inform clinical treatment of such partial tears. It is unknown how injury partial injury impacts long-term degenerative changes in the joint relative to complete injury. In this study, we hypothesized that partial (anteromedial (AM) or posterolateral (PL) bundle) tears would result in small levels of instability and degeneration relative to complete ACL tears and that the degree of degeneration would associate with joint instability.

Design: Partial (isolated AM or PL bundle) or complete ACL injury was arthroscopically created in 3-month-old juvenile pigs. The contralateral limb served as a sham-operated control. Six months after injury, joint biomechanics was assessed along with cartilage and meniscus degeneration (via magnetic resonance imaging [MRI], gross imaging, and histology).

Results: Joint laxity increases were minimal after PL bundle injury (difference relative to controls (confidence interval): 0.5 (-1.2-2.2) mm), minor after AM bundle injury (3.7 (2.0-5.4) mm), and major after ACL injury (15.8 (13.7-17.8) mm). Cartilage MRI T1ρ relaxation times increased minimally after PL bundle injury (-0.9 (-5.1-3.3) ms for lateral tibia), moderately after AM bundle injury (6.6 (1.7-11.4) ms), and substantially after ACL injury (10.8 (2.1-19.5) ms). Changes in meniscus volume followed a similar rank order. Degeneration was associated with the extent of joint destabilization.

Conclusions: These findings suggest that cartilage and meniscus degeneration in the skeletally immature joint are associated with joint laxity after partial and complete ACL injuries.

Objectives: To investigate the course of restrictions in paid and unpaid work and corresponding societal costs in patients with hand osteoarthritis (OA).

Methods: Patients with data of at least baseline and one follow-up moment (year one up to year eight) of the Dutch Hand OSTeoArthritis in Secondary care cohort (HOSTAS) were included. The Health and Labour Questionnaire was used to assess over the last two weeks hand OA-related restrictions for paid and unpaid work. Societal costs of productivity loss were estimated with Dutch government data on 2021.

Results: 351 patients were included (mean age 60 years, 84% women). At baseline, 166/351 (47%) had paid work, decreasing to 54/164 (33%) at year eight. Loss of productive time over the two-week period was reported by 32/166 (19%) patients with paid work at baseline, 17/104 (16%) at year four, among whom 12/104 (11%) patients at both moments. Any restrictions over this two-week period were experienced by 89/166 patients (54%) at baseline and 41/104 (39%) at year four for those with paid work. Regarding unpaid work, 157/351 (45%) reported replacement of tasks by others at baseline and 72/164 (44%) at year eight. 205/351 (59%) reported restrictions at baseline, and 99/164 (60%) at year eight. Mean total societal costs for loss of paid and unpaid work were, per patient, €89/two weeks (95% confidence interval 52;127) at baseline and €47/two weeks (26;69) at year eight.

Conclusions: The proportion of patients with paid work decreases during follow-up, but restrictions at paid and unpaid work seem mostly stable.