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Anterior cruciate ligament (ACL) injury, a common sports injury, is associated with a high risk of subsequent osteoarthritis (OA), which can cause serious pain and disability. Understanding the detailed mechanism underlying the predisposition of knee with ACL injury to secondary OA at an early stage is key to preventing future degradation and progression to a clinically significant disease. A total of 56 male Sprague Dawley rats (age, 8 weeks; weight, 180-220 g) were randomly divided into three experimental groups: control, ACL transection (ACLT; where surgical procedure was performed with ACLT), and sham (where surgical procedure was performed without ACLT). The ACLT and sham groups were further divided into three subgroups based on when the rats were sacrificed: 4, 8, and 12 weeks after the surgical procedure. The control group and the aforementioned subgroups contained 8 rats each. We used nuclear magnetic resonance (NMR)-based metabolomic analysis to analyze rat serum samples for the metabolic characteristics and the underlying mechanisms. In total, 28 metabolites were identified in the NMR spectra of the rat sera. At 4 and 8 weeks postoperatively, the sham group demonstrated metabolic profiles different from those of the ACLT group. However, this difference was not observed 12 weeks postoperatively. In total, five metabolites (acetate, succinate, sn-glycero-3-phosphocholine, glucose, and phenylalanine) and five metabolic pathways (phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; pyruvate metabolism; starch and sucrose metabolism; and histidine metabolism) demonstrated significant differences between the ACLT and sham groups. ACL injury was noted to considerably affect biochemical homeostasis and metabolism; however, these metabolic changes persisted briefly. Moreover, glucose was a characteristic metabolite, and several energy-related metabolic pathways were significantly disturbed. Therefore, an ACL injury may lead to considerable impairments in energy metabolism. Abnormal glucose levels facilitate chondrocyte function impairment and thereby lead to OA progression. Furthermore, lactate may aid in identifying metabolic changes specific to knee trauma not related to an ACL injury. Overall, the metabolic changes in rat serum after an ACL injury were closely related to disturbances in energy metabolism and amino acid metabolism. The current results may aid in understanding the pathogenesis of posttraumatic osteoarthritis., (© 2023. The Author(s).)

Osteoarthritis (OA) represents the most prevalent and disabling arthritis worldwide due to its heterogeneous and progressive articular degradation. However, effective and timely diagnosis and fundamental treatment for this disorder are lacking. Metabolomics, a growing field in life science research in recent years, has the potential to detect many metabolites and thus explains the underlying pathophysiological processes. Hence, new specific metabolic markers and related metabolic pathways can be identified for OA. In this review, we aimed to provide an overview of studies related to the metabolomics of OA in animal models and humans to describe the metabolic changes and related pathways for OA. The present metabolomics studies reveal that the pathogenesis of OA may be significantly related to perturbations of amino acid metabolism. These altered amino acids (e.g., branched-chain amino acids, arginine, and alanine), as well as phospholipids, were identified as potential biomarkers to distinguish patients with OA from healthy individuals.

Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest possible mechanisms thought to be responsible for PTOA, evaluate current diagnostic methods for detecting early OA, and discuss potential interventions to combat PTOA. We also identify important directions for future research. Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments. A number of factors are thought to be involved in the underlying mechanism, including structural factors, biological factors, mechanical factors, and neuromuscular factor. Since there is a clear "start point" for PTOA, early detection and intervention is of great importance. Currently, imaging modalities and specific biomarkers allow early detection of PTOA. However, none of them is both sensitive and easily accessible. After ACL injury, many patients undergo surgical reconstruction of ACL to restore joint stability and prevent excessive loading. However, convincing evidence is still lacking for the superiority of ACL-R to conservative management in term of the incidence of PTOA. As for non-surgical treatment such as anti-cytokine and chemokine interventions, most of them are investigated in animal studies and have not been applied to humans. A complete understanding of mechanisms to stratify the patients into different subgroups on the basis of risk factors is critical. And the improvement of standardized and quantitative assessment techniques is necessary to guide intervention. Moreover, treatments targeted toward different pathogenic pathways may be crucial to the management of PTOA in the future.

Studies investigating the effect of running on risk for developing osteoarthritis at weight-bearing joints have reported with conflicting results. Generally, moderate-level running is not likely detrimental to joint health. However, many factors may be associated with the increased risk of developing osteoarthritis in runners. Factors often implicated in the development of osteoarthritis comprise those that increase joint vulnerability and those which increase joint loading. It is therefore suggested that running has different effects on different people. Efforts should be made to identify those with joint vulnerability and joint loading, and measures should be taken to have those factors and/or their running programs modified to run safely. Further investigations are needed to examine the effect of running on joint health under different conditions to confirm the association between exposure to risk factors and development of osteoarthritis, as well as to validate the effectiveness of measures for preventing running-related osteoarthritis.

Depression, one of the most common comorbidities with osteoarthritis (OA), affects patient prognosis and quality of life. It also increases the overall burden of disease. This subgroup of patients has not been effectively managed in clinical settings. The study aimed to direct physicians' attention to the co-occurrence of depression and OA. Therefore, this review summarizes the relevant literature published over the past 10 years. The focus is on the prevalence of and risk factors for depression in OA, the effects of depression on OA development and treatment response, comorbidity mechanisms, screening, and non-pharmacological treatment. The research on the etiology of depression has been driven largely by epidemiological studies. Recent studies have shown that high levels of pain, poor levels of function, high numbers of OA sites, and slow gait might be associated with depression. However, the pathophysiology of OA and depression comorbidities remains unclear. In addition to immune inflammation and structural changes in the brain, which have been documented in brain imaging studies, psychosocial factors may also play a role. The evidence indicates that depression can be treated with early intervention; however, adjustments may need to be made for individuals with comorbid depression in OA. It is recommended that health care providers pay more attention to depressive symptoms in patients with OA. Clinicians should develop and implement an individualized and comprehensive treatment plan for patients based on a mental health assessment and in teams with other professionals to optimize treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: To compare the pathological changes in cartilage derived from rats that developed osteoarthritis either by joint immobilization or by strenuous treadmill running in order to better understand their respective pathomechanism. Method: A total of 24 male Wistar rats were randomly assigned to three groups: sedentary control (CON), immobilization (IM), and strenuous running (SR). For rats in the IM group, unilateral knee joint was immobilized in flexion. Rats in the SR group underwent treadmill running with high intensity. Eight weeks later, all animals were sacrificed. Femoral condyles were collected to take histological observation for cartilage characteristic and immunohistochemistry for collagen type II. In addition, cartilage samples were obtained to assess gene expression of aggrecan, collagen type II, biglycan, and fibromodulin by quantitative RT-PCR. Results: Gross and histological observation showed osteoarthritic changes in groups SR and IM; however, more severe cartilage degradation was revealed in the latter. Proteoglycan and collagen II content decreased in groups SR and IM in comparison to group CON, with more loss in group IM. In group SR, mRNA levels in femoral cartilage were found to be unaltered for all the molecules measured. On the contrary, these molecules were significantly downregulated in group IM. Conclusion: Differences in gross observation, histological characteristics, and gene expression of proteoglycans and collagen II suggest that both knee immobilization and strenuous running would lead to degenerative change of cartilage, but at different stages of the degenerative process. [ABSTRACT FROM PUBLISHER]

Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present study investigated the effects of excessive mechanically stretched osteoblasts on the metabolism and apoptosis of chondrocytes, and also assessed the involvement of the Wnt/β-catenin signaling pathway. In the present study, rat chondrocytes and osteoblasts were subjected to mechanical tensile strain, and an indirect chondrocyte-osteoblast co-culture model was established. Reverse transcription-quantitative PCR and western blotting were performed to determine the expression levels of genes and proteins of interest. An ELISA was performed to investigate the levels of cytokines, including matrix metalloproteinase (MMP) 13, MMP 3, interleukin-6 (IL-6) and prostaglandin E2 (PG E2), released from osteoblasts. Flow cytometry was performed to detect the apoptosis of chondrocytes exposed to stretched osteoblast conditioned culture medium. The levels of MMP 13, IL-6 and PG E2 increased significantly in the supernatants of stretched osteoblasts compared with the un-stretched group. By contrast, the mRNA expression levels of Collagen 1a and alkaline phosphatase were significantly decreased in osteoblasts subjected to mechanical stretch compared with the un-stretched group. The mRNA expression level of Collagen 2a was significantly decreased, whereas the expression levels of MMP 13 and a disintegrin and metalloproteinase with thrombospondin-like motifs 5 were significantly increased in chondrocytes subjected to mechanical stretch compared with the un-stretched group. In the co-culture model, the results indicated that excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes, which was partly inhibited by Wnt inhibitor XAV-939. The results of the present study demonstrated that excessive mechanical stretch led to chondrocyte degradation and inhibited osteoblast osteogenic differentiation; furthermore, excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]