Choice of Acromioclavicular Dislocation Treatment Should Not Be Influenced by Risk of Development of Acromioclavicular Osteoarthritis: A Systematic Review With Meta-Analysis.

BACKGROUND: It is currently unknown to what degree surgical or nonoperative treatment of acromioclavicular (AC) dislocation influences the development of osteoarthritis (OA). The aim of this study was to evaluate AC OA after surgical and nonoperative treatment for AC dislocations, compare OA prevalence between treatment options, and compare OA prevalence between the injured and contralateral shoulder. METHODS: Articles reporting on the prevalence of OA after surgical or nonoperative treatment of an AC dislocation with a minimal 2-year follow-up were included. AC OA presence was extracted for the injured and contralateral shoulder. Treatment categories were defined based on anatomical variation in the reattachment of ligaments: AC fixation, coracoclavicular (CC) fixation, AC and CC fixation, Bosworth screw synthetic graft, tendon graft, and conservative. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. RESULTS: Ninety-four articles were included for qualitative analysis, and 7 articles were included for meta-analysis (n = 3,812; follow-up = 2.0-24.2 years; mean age 37.6 ± 10.4 years). A total of 3,483 patients underwent surgical treatment, and 329 patients underwent conservative treatment. OA prevalence ranged from 6.7%-29.3% between 7 pooled treatment categories. Most included studies had a follow-up <10 years (94%) and OA prevalence increased with time, regardless of treatment option. There was no difference in OA prevalence between the injured and contralateral shoulder (p = 0.120). MINORS scores were varied, ranging from poor to very good. CONCLUSION: The pooled AC OA prevalence of the 7 treatment categories ranged from 6.7% for the CC fixation surgical group to 29.3% for the conservative treatment group. However, the included studies were predominantly of low quality and had varying follow-up periods, with most having relatively short follow-up durations. No difference in AC OA prevalence was found between the injured and contralateral shoulder. Based on the available evidence, treatment choice for AC dislocation should not be influenced by the potential development of AC AO. LEVEL OF EVIDENCE: Level IV. See Instructions for Authors for a complete description of levels of evidence.

Long-term outcomes after capitate fractures: a median 16-year follow-up.

INTRODUCTION: The long-term effects of a capitate fracture are unknown. The aim of this study was to assess both clinical and radiological long-term outcomes after a capitate fracture. MATERIALS AND METHODS: From a cohort of 526 consecutive patients with post traumatic radial sided wrist pain, 23 were identified diagnosed with a capitate fracture. 16 of these (11 males and 5 females) with a median age at injury of 17.5 years (range 11-27 years) were eligible for a follow-up after a median of 16 years (range 8 to 17 years). In this study patients were examined using conventional radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) at the time of injury and with CT at the follow-up. At follow-up radiological signs of osteoarthritis were graded in four stages and clinical outcome was evaluated by measuring range of wrist motion and grip and pinch strength. The subjective outcome was assessed using DASH and PRWE questionnaires. RESULTS: Five patients had isolated capitate fractures and 11 had concomitant fractures, 10 of which had a simultaneous scaphoid fracture. 14 patients had been treated non-surgically in a cast and two patients were treated surgically. None of the fractures were visible on conventional radiographs at the time of injury. At follow-up all fractures had healed without signs of avascular necrosis. In one patient, CT examination revealed osteoarthritis between the capitate and lunate. This did not cause clinical symptoms. Functional impairments and pain scores were low: median DASH score 0, median PRWE 3 and median VAS pain score 0. We found no impairment in range of motion or grip and pinch strength. CONCLUSIONS: At a median of 16-year follow-up, patients with a capitate fracture report normal self-assessed hand function as well as good wrist motion and strength. The risk of development of posttraumatic arthritis in the joints around the capitate is low.

TIPE2 gene transfer ameliorates aging-associated osteoarthritis in a progeria mouse model by reducing inflammation and cellular senescence.

Osteoarthritis (OA) pain is often associated with the expression of tumor necrosis factor alpha (TNF-α), suggesting that TNF-α is one of the main contributing factors that cause inflammation, pain, and OA pathology. Thus, inhibition of TNF-α could potentially improve OA symptoms and slow disease progression. Anti-TNF-α treatments with antibodies, however, require multiple treatments and cannot entirely block TNF-α. TNF-α-induced protein 8-like 2 (TIPE2) was found to regulate the immune system's homeostasis and inflammation through different mechanisms from anti-TNF-α therapies. With a single treatment of adeno-associated virus (AAV)-TIPE2 gene delivery in the accelerated aging Zmpste24-/- (Z24-/-) mouse model, we found differences in Safranin O staining intensity within the articular cartilage (AC) region of the knee between TIPE2-treated mice and control mice. The glycosaminoglycan content (orange-red) was degraded in the Z24-/- cartilage while shown to be restored in the TIPE2-treated Z24-/- cartilage. We also observed that chondrocytes in Z24-/- mice exhibited a variety of senescent-associated phenotypes. Treatment with TIPE2 decreased TNF-α-positive cells, ß-galactosidase (ß-gal) activity, and p16 expression seen in Z24-/- mice. Our study demonstrated that AAV-TIPE2 gene delivery effectively blocked TNF-α-induced inflammation and senescence, resulting in the prevention or delay of knee OA in our accelerated aging Z24-/- mouse model.

Risk of Upper Limb Diseases in Osteoarthritis Patients: A Propensity-score-matched Cohort Study.

BACKGROUND/AIM: Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts quality of life, particularly when affecting the hands. However, whether patients with OA are associated with higher risk of developing upper limb disorders, specifically trigger finger (TF) and carpal tunnel syndrome (CTS), remains unclear. This study aimed to evaluate the risk of upper limb disease in OA patients. PATIENTS AND METHODS: Using the US Collaborative Network, a subset of the TriNetX research network, we identified patients diagnosed with OA and matched them 1:1 with non-OA controls based on propensity scores. Matching covariates included age, sex, race, and comorbidities. The cohort consisted of 1,554,182 patients in each group. The hazard ratio of TF and CTS, as well as related surgical interventions, was assessed over a 5-year follow-up period. RESULTS: Patients with OA had a 1.30-fold increased risk of TF [95% confidence interval (CI)=1.27-1.33] and a 1.50-fold increased risk of CTS (95%CI=1.48-1.53) compared to controls. The hazard ratios for undergoing surgical interventions were 1.61 for TF (95%CI=1.51-1.71) and 1.97 for CTS (95%CI=1.78-2.19). These risks remained significant across various sensitivity analyses and stratifications according to age and sex. CONCLUSION: OA significantly increases the risk of TF and CTS. These findings highlight the need for vigilant monitoring and management of upper limb disorders in OA patients to improve overall patient care and outcomes. Future research is warranted to focus on pathological mechanisms of OA and their impact on upper limb health to develop targeted interventions.

Angiogenesis unveiled: Insights into its role and mechanisms in cartilage injury.

Osteoarthritis (OA) commonly results in compromised mobility and disability, thereby imposing a significant burden on healthcare systems. Cartilage injury is a prevalent pathological manifestation in OA and constitutes a central focus for the development of treatment strategies. Despite the considerable number of studies aimed at delaying this degenerative process, their outcomes remain unvalidated in preclinical settings. Recently, therapeutic strategies focused on angiogenesis have attracted the growing interest from researchers. Thus, we conducted a comprehensive literature review to elucidate the current progress in research and pinpoint research gaps in this domain. Additionally, it provides theoretical guidance for future research endeavors and the development of treatment strategies.

NUMB attenuates posttraumatic osteoarthritis by inhibiting BTRC and inactivating the NF-κB pathway.

Posttraumatic osteoarthritis (PTOA) is closely related to the inflammatory response caused by mechanical injury and leads to joint degeneration. Herein, we aimed to evaluate the role and underlying mechanism of NUMB in PTOA progression. Anterior cruciate ligament transection (ACLT)-induced rats and interleukin (IL)-1ß-treated chondrocytes were used as in vivo and in vitro models of PTOA, respectively. The NUMB overexpression plasmid (pcDNA-NUMB) was administered by intra-articular injection to PTOA model rats, and safranin O-fast green staining, the Osteoarthritis Research Society International (OARSI) scoring system, and HE staining were used to evaluate the severity of cartilage damage. The secretion of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and chondrocyte-specific markers (MMP13 and COL2A1) was detected via ELISA. Cell viability and apoptosis were evaluated by MTT and TUNEL assays. NUMB was expressed at lower levels in ACLT-induced PTOA rats and in IL-1ß-treated chondrocytes than in control rats and cells. NUMB overexpression enhanced cell viability and reduced cell apoptosis, inflammation and cartilage degradation in chondrocytes stimulated by IL-1ß. NUMB bound to BTRC to promote p-IκBα expression, resulting in NF-κB pathway inactivation. BTRC overexpression reversed the promoting effect of NUMB overexpression on cell viability and the inhibitory effects of NUMB overexpression on apoptosis, inflammation and cartilage degradation in IL-1ß-induced chondrocytes. In addition, overexpression of NUMB alleviated articular cartilage damage by repressing inflammation and cartilage degradation in ACLT-induced PTOA rats. Our data indicated that NUMB regulated PTOA progression through the BTRC/NF-κB pathway, which may be a viable therapeutic target in PTOA.

A case of Melkersson-Rosenthal syndrome with temporomandibular joint osteoarthritis: multidisciplinary treatment and autoimmune etiological hypothesis.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement. CASE PRESENTATION: This paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis. CONCLUSIONS: These findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

PLCγ1 deficiency in chondrocytes accelerates the age-related changes in articular cartilage and subchondral bone.

Ageing is the most prominent risk for osteoarthritis (OA) development. This study aimed to investigate the role of phosphoinositide-specific phospholipase Cγ (PLCγ) 1, previously linked to OA progression, in regulating age-related changes in articular cartilage and subchondral bone. d-galactose (d-Gal) was employed to treat chondrocytes from rats and mice or injected intraperitoneally into C57BL/6 mice. RTCA, qPCR, Western blot and immunohistochemistry assays were used to evaluate cell proliferation, matrix synthesis, senescence genes and senescence-associated secretory phenotype, along with PLCγ1 expression. Subchondral bone morphology was assessed through micro-CT. In mice with chondrocyte-specific Plcg1 deficiency (Plcg1flox/flox; Col2a1-CreERT), articular cartilage and subchondral bone were examined over different survival periods. Our results showed that d-Gal induced chondrocyte senescence, expedited articular cartilage ageing and caused subchondral bone abnormalities. In d-Gal-induced chondrocytes, diminished PLCγ1 expression was observed, and its further inhibition by U73122 exacerbated chondrocyte senescence. Plcg1flox/flox; Col2a1-CreERT mice exhibited more pronounced age-related changes in articular cartilage and subchondral bone compared to Plcg1flox/flox mice. Therefore, not only does d-Gal induce senescence in chondrocytes and age-related changes in articular cartilage and subchondral bone, as well as diminished PLCγ1 expression, but PLCγ1 deficiency in chondrocytes may also accelerate age-related changes in articular cartilage and subchondral bone. PLCγ1 may be a promising therapeutic target for mitigating age-related changes in joint tissue.

Post-Traumatic Arthritis of the Knee and Ankle.

Post-traumatic osteoarthritis (PTOA) occurs following injury to joints. It accounts for approximately 12% of osteoarthritis and has far-reaching effects on individual patients and social/health care systems. Present work focuses on evaluating the role of the post-traumatic inflammatory response in the development and progression of the disease. As there is minimal evidence to suggest the capacity of cartilage to undergo self-healing, most of this work focuses strictly on the avoidance or prevention of PTOA as opposed to treatment solutions following its onset. Ongoing and future investigations may reveal therapeutic targets for possible intervention and ultimately the prophylaxis of PTOA development.

An HFD negatively influences both joint and liver health in rabbits with and without an enzymatically-induced model of arthritis.

Osteoarthritis (OA) is a common arthritis types in animals that causes persistent pain and reduces quality of life. Although a high-fat diet (HFD) is widely believed to induce obesity and have adverse effects on the body, the connection between HFD and joint health is not well understood. Therefore, in this study, 32 healthy male New Zealand rabbits were randomly divided into four groups: healthy rabbits fed a standard diet (NDG, n=8) or an HFD (HDG, n=8), rabbits fed a standard diet (OAG, n=8) and an HFD (HOG, n=8), and arthritis was induced by intra-articular enzyme injection. After 12 weeks of HFD feeding, articular cartilage, synovium, and subchondral bone were isolated and collected. Joint tissue damage was evaluated using histopathological and imaging tests. The results showed that there was no significant difference in body weight between rabbits fed a normal diet and those fed an HFD. However, the HFD led to an increase in joint injuries in both induced and non-induced arthritis rabbits. Specifically, the HFD induced lipid metabolism disorders and liver damage in vivo, significantly elevating the levels of serum inflammatory cytokines and bone metabolism markers. Moreover, HFD exacerbated articular cartilage damage in the joints and increased the accumulation of inflammatory cells in synovial tissue, resulting in a notable increase in synovial macrophages and inflammatory cytokines. Additionally, HFD accelerated the bone resorption process in subchondral bone, leading to the destruction of bone mass and subchondral bone microstructure. In summary, the results of this study indicate that an HFD can cause histological damage to the articular cartilage, synovium, and subchondral bone in rabbits, exacerbating arthritis in pre-existing joint damage. Notably, weight is not the primary factor in this effect.

Osteoarthritis as a Systemic Disease Promoted Prostate Cancer In Vivo and In Vitro.

Osteoarthritis (OA) is increasing worldwide, and previous work found that OA increases systemic cartilage oligomeric matrix protein (COMP), which has also been implicated in prostate cancer (PCa). As such, we sought to investigate whether OA augments PCa progression. Cellular proliferation and migration of RM1 murine PCa cells treated with interleukin (IL)-1α, COMP, IL-1α + COMP, or conditioned media from cartilage explants treated with IL-1α (representing OA media) and with inhibitors of COMP were assessed. A validated murine model was used for tumor growth and marker expression analysis. Both proliferation and migration were greater in PCa cells treated with OA media compared to controls (p < 0.001), which was not seen with direct application of the stimulants. Migration and proliferation were not negatively affected when OA media was mixed with downstream and COMP inhibitors compared to controls (p > 0.05 for all). Mice with OA developed tumors 100% of the time, whereas mice without OA only 83.4% (p = 0.478). Tumor weight correlated with OA severity (Pearson correlation = 0.813, p = 0.002). Moreover, tumors from mice with OA demonstrated increased Ki-67 expression compared to controls (mean 24.56% vs. 6.91%, p = 0.004) but no difference in CD31, PSMA, or COMP expression (p > 0.05). OA appears to promote prostate cancer in vitro and in vivo.

Establishment of a Posttraumatic Osteoarthritis Model in Mice Induced by Noninvasive Anterior Cruciate Ligament Tear.

BACKGROUND: Animal models that use open surgical transection of the anterior cruciate ligament (ACL) do not accurately simulate the clinical condition regarding the pivot-shift mechanism and the associated inflammatory response that occurs before reconstruction. PURPOSE/HYPOTHESIS: The purpose was to characterize a reproducible manual, nonsurgical method to mimic an isolated ACL tear in a clinically relevant model and to evaluate the development of progressive posttraumatic osteoarthritis due to ACL injury. It was hypothesized that the ACL could be reproducibly torn with minimal damage to other ligaments and that there would be progressive development of degenerative joint disease after ACL injury. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 37 mice (strain C57BL/6) were used to compare the manual procedure with sham surgery (sham group; n = 10) and with the established surgical ACL transection (ACLT) procedure (surgical group; n = 27). In the sham group, a closed manual procedure was performed on the right knee and sham surgery on the left knee. In the surgical group, the closed manual procedure was performed on the right knee and surgical ACLT on the left knee. Dissection using India ink, histological assessment with safranin O and hematoxylin-eosin staining, radiological evaluation through radiographs and microfocus computed tomography scans, and gait analyses were performed to assess cartilage/ligament status. Osteoarthritis Research Society International (OARSI) and synovitis scores, anterior tibial translation, range of motion, bone microstructure, osteophyte volume, and pain were assessed at 2, 4, and 8 weeks postoperatively. RESULTS: The manual procedure successfully resulted in an ACL rupture and associated meniscal injury. The posterior cruciate, lateral collateral, and medial collateral ligaments were intact in all dissected knees. Two weeks after ACL tear, the surgical group showed a significantly higher synovitis score, whereas 8 weeks after ACL tear, the manual group showed a significantly higher volume of osteophytes. No significant differences were found between the groups in terms of OARSI score, anterior tibial translation, range of motion, bone microstructure computed tomography values, and stride distance/irregularity. CONCLUSION: This procedure can be used to create an ACL tear model without causing grossly evident injuries to other ligaments and avoiding the risk of cartilage damage from surgical instruments. CLINICAL RELEVANCE: This procedure offers a more clinically relevant ACL tear model and facilitates simple, inexpensive, and reproducible development of posttraumatic osteoarthritis.

[Influence and risk factors of lateral hinge fracture on early effectiveness of supramalleolar osteotomy].

Objective: To evaluate the influence of lateral hinge fracture (LHF) on the early effectiveness of supramalleolar osteotomy (SMO) and to explore the related risk factors for LHF. Methods: A total of 39 patients (39 feet) with varus-type ankle osteoarthritis treated with SMO between January 2016 and December 2022 were analyzed retrospectively. There were 10 males and 29 females, aged from 41 to 71 years (mean, 57.7 years). According to Takakura stage, there were 6 feet in stage Ⅱ, 19 feet in stage Ⅲa, and 14 feet in stage Ⅲb. The LHF was recognized by the immediate postoperative X-ray film. The osteotomy healing time and the changes of pain visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, tibial anterior surface angle (TAS), tibial lateral surface angle (TLS), and tibiotalar angle (TT) before and after operation were compared between patients with and without LHF. The age, gender, affected side, body mass index, Takakura stage, preoperative VAS score, preoperative AOFAS score, preoperative TAS, preoperative TLS, preoperative TT, SMO correction angle, osteotomy distraction, distance from medial osteotomy to ankle joint line (MD), and distance from lateral osteotomy to ankle joint line (LD) were compared between with and without LHF patients, and further logistic regression analysis was used to screen the risk factors of LHF during SMO. Results: All patients were followed up 12-54 months (mean, 27.1 months). During operation, 13 feet developed LHF (group A) and 26 feet did not develop LHF (group B). X-ray film reexamination showed that 1 patient in group A complicated with tibial articular surface cleft fracture had delayed osteotomy and healed successfully after plaster fixation; the osteotomy of other patients healed, and there was no significant difference in healing time between the two groups ( P>0.05). At last follow-up, there were significant differences in VAS score, AOFAS score, TAS, TLS, and TT of the two groups when compared with preoperative ones ( P<0.05), but there was no significant difference in the changes of above indicators before and after operation between the two groups ( P>0.05). The differences in SMO correction angle, osteotomy distraction, and LD between with and without LHF patients were significant ( P<0.05), and further logistic regression analysis showed that excessive LD was the risk factor of LHF during SMO ( P<0.05). Conclusion: Too high or too low lateral hinge position during SMO may lead to LHF, but as long as appropriate treatment and rehabilitation measurements are taken, the early effectiveness is similar to that of patients without LHF.

Effects of sex differences on osteoarthritic changes after anterior cruciate ligament reconstruction in rats.

The prevalence of primary osteoarthritis is higher in females than males. However, it remains unclear if there are sex differences in the incidence of post-traumatic osteoarthritis after anterior cruciate ligament (ACL) reconstruction. In this study, we aimed to investigate the effects of sex on osteoarthritic changes after ACL reconstruction using an animal model. Rats were divided into the following four groups: male control, male ACL reconstruction, female control, and female ACL reconstruction. ACL reconstruction surgery was performed on the right knees of rats in the ACL reconstruction groups, while rats in the control groups did not undergo knee surgery. At 1, 4, and 12 weeks after surgery, cartilage degeneration in the medial tibial plateau and osteophyte formation in the proximal tibia were histologically assessed. After ACL reconstruction, an increase in the Mankin score, cartilage fissures, and osteophyte formation were detected within 12 weeks in both male and female rats, with similar degrees of these changes between males and females. However, changes in cartilage thickness and chondrocyte density after ACL reconstruction differed between males and females. Cartilage thickening was observed in male rats but not in female rats. The increase in chondrocyte density in the anterior region was detected in both males and females but was more pronounced in female rats. In conclusion, osteoarthritic changes were observed after ACL reconstruction in both male and female rats, but differences in changes in cartilage thickness and chondrocyte density were observed between males and females.

Hyperthyroidism increases the risk of osteoarthritis in individuals aged 60-80 years.

To elucidate the currently unknown relationship between hyperthyroidism and osteoarthritis (OA). During 2007-2012, 7,433 participants (hyperthyroidism patients = 125; OA patients = 675) were included in the National Health and Nutrition Examination Survey database. We used a weighted multivariable-adjusted logistic regression analysis to assess the association between hyperthyroidism and OA. We also assessed the causality of that relationship using publicly available genome-wide association study data and three Mendelian randomization (MR) analysis methods. The heterogeneity test, pleiotropy test, and leave-one-out tests were used for sensitivity analysis. In this cross-sectional study, after adjusting for potential confounding factors, we found that hyperthyroidism significantly (P = 0.018) increased the risk of OA (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.2-4.17). Age-stratified analysis revealed that hyperthyroidism was associated with a greater risk of OA in the 60-80-year-old age group (OR = 2.86, 95% CI = 1.46-5.59, P = 0.002), with no significant association in the 18-59-year-old age group (all P > 0.05). The results of the inverse-variance weighting (IVW) analysis showed that hyperthyroidism increased the risk of OA (OR = 1.23, 95% CI = 1.04-1.46; P = 0.017). The weighted median estimator (WME) and MR-Egger method also confirmed this causal association (OR = 1.27 and OR = 1.32, respectively). The sensitivity analysis results confirmed the reliability of this conclusion. In addition, IVW-based reverse-MR analysis revealed that OA did not increase the risk of hyperthyroidism (OR = 1.02, 95% CI = 0.97-1.08; P = 0.449). Hyperthyroidism is associated with an increased risk of OA, but the underlying pathological mechanism still needs to be clarified in future research.

Potential Roles of Inflammation on Post-Traumatic Osteoarthritis of the Ankle.

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated. Inflammatory processes triggered by intra-articular ankle fractures have emerged as potential instigators that expedite the progression of PTOA. Injury to the articular cartilage and subchondral bone may lead to the release of inflammatory mediators, which can contribute to cartilage degradation and bone resorption. This study provides a narrative review on the current knowledge concerning the association between inflammation and the development of PTOA following intra-articular ankle fractures. We also discuss novel therapeutic agents that target inflammatory pathways to impede the progression of post-traumatic osteoarthritis after intra-articular ankle fractures. These medication and interventions were summarized within this review article.

Assessing the causal relationship of birth weight and childhood obesity on osteoarthritis: a Mendelian randomization study.

Obesity is associated with osteoarthritis (OA), but few studies have used fetal origin to explore the association. Our study aims to disentangle the causality between birth weight, childhood obesity, and adult OA using Mendelian randomization (MR). We identified single nucleotide polymorphisms (SNPs) related to birth weight (n = 298,142) and childhood obesity (n = 24,160) from two genome-wide association studies contributed by the Early Growth Genetics Consortium. Summary statistics of OA and its phenotypes (knee, hip, spine, hand, thumb, and finger OA) from the Genetics of Osteoarthritis Consortium (n = 826,690) were used to estimate the effects of SNPs on OA. Multivariable MR (MVMR) was conducted to investigate the independent effects of exposures. It turned out that genetically predicted standard deviation increase in birth weight was not associated with OA. In contrast, there was a marginally positive effect of childhood obesity on total [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.00, 1.15 using IVW], knee (OR = 1.13, 95% CI = 1.05, 1.22 using weighted median), hip (OR = 1.13, 95% CI = 1.04, 1.24 using IVW), and spine OA (OR = 1.12, 95% CI = 1.03, 1.22 using IVW), but not hand, thumb, or finger OA. MVMR indicated a potential adulthood body mass index-dependent causal pathway between childhood obesity and OA. In conclusion, no association of birth weight with OA was suggested. Childhood obesity, however, showed a causality with OA in weight-bearing joints, which seems to be a general association of obesity with OA.

Exercise following joint distraction inhibits muscle wasting and delays the progression of post-traumatic osteoarthritis in rabbits by activating PGC-1α in skeletal muscle.

OBJECTIVE: Muscle wasting frequently occurs following joint trauma. Previous research has demonstrated that joint distraction in combination with treadmill exercise (TRE) can mitigate intra-articular inflammation and cartilage damage, consequently delaying the advancement of post-traumatic osteoarthritis (PTOA). However, the precise mechanism underlying this phenomenon remains unclear. Hence, the purpose of this study was to examine whether the mechanism by which TRE following joint distraction delays the progression of PTOA involves the activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as its impact on muscle wasting. METHODS: Quadriceps samples were collected from patients with osteoarthritis (OA) and normal patients with distal femoral fractures, and the expression of PGC-1α was measured. The hinged external fixator was implanted in the rabbit PTOA model. One week after surgery, a PGC-1α agonist or inhibitor was administered for 4 weeks prior to TRE. Western blot analysis was performed to detect the expression of PGC-1α and Muscle atrophy gene 1 (Atrogin-1). We employed the enzyme-linked immunosorbent assay (ELISA) technique to examine pro-inflammatory factors. Additionally, we utilized quantitative real-time polymerase chain reaction (qRT-PCR) to analyze genes associated with cartilage regeneration. Synovial inflammation and cartilage damage were evaluated through hematoxylin-eosin staining. Furthermore, we employed Masson's trichrome staining and Alcian blue staining to analyze cartilage damage. RESULTS: The decreased expression of PGC-1α in skeletal muscle in patients with OA is correlated with the severity of OA. In the rabbit PTOA model, TRE following joint distraction inhibited the expressions of muscle wasting genes, including Atrogin-1 and muscle ring finger 1 (MuRF1), as well as inflammatory factors such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in skeletal muscle, potentially through the activation of PGC-1α. Concurrently, the production of IL-1ß, IL-6, TNF-α, nitric oxide (NO), and malondialdehyde (MDA) in the synovial fluid was down-regulated, while the expression of type II collagen (Col2a1), Aggrecan (AGN), SRY-box 9 (SOX9) in the cartilage, and superoxide dismutase (SOD) in the synovial fluid was up-regulated. Additionally, histological staining results demonstrated that TRE after joint distraction reduced cartilage degeneration, leading to a significant decrease in OARSI scores.TRE following joint distraction could activate PGC-1α, inhibit Atrogin-1 expression in skeletal muscle, and reduce C-telopeptides of type II collagen (CTX-II) in the blood compared to joint distraction alone. CONCLUSION: Following joint distraction, TRE might promote the activation of PGC-1α in skeletal muscle during PTOA progression to exert anti-inflammatory effects in skeletal muscle and joint cavity, thereby inhibiting muscle wasting and promoting cartilage regeneration, making it a potential therapeutic intervention for treating PTOA.