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Tendons transmit the muscle contraction forces to bones and drive joint movement throughout life. While extensive research have indicated the essentiality of mechanical forces on tendon development, a comprehensive understanding of the fundamental role of mechanical forces still needs to be impaerted. This scoping review aimed to summarize the current knowledge about the role of mechanical forces during the tendon developmental phase. The electronic database search using PubMed, performed in May 2023, yielded 651 articles, of which 16 met the prespecified inclusion criteria. We summarized and divided the methods to reduce the mechanical force into three groups: loss of muscle, muscle dysfunction, and weight‐bearing regulation. In contrast, there were few studies to analyze the increased mechanical force model. Most studies suggested that mechanical force has some roles in tendon development in the embryo to postnatal phase. However, we identified species variability and methodological heterogeneity to modulate mechanical force. To establish a comprehensive understanding, methodological commonality to modulate the mechanical force is needed in this field. Additionally, summarizing chronological changes in developmental processes across animal species helps to understand the essence of developmental tendon mechanobiology. We expect that the findings summarized in the current review serve as a groundwork for future study in the fields of tendon developmantal biology and mechanobiology. Key Findings: Recent mechano‐biological studies about tendon development have no consensus on the definition of mechanical force on the tendon. A clear definition of mechanical force based on species is needed to establish a comprehensive understanding of the role of mechanical force on tendon development. [ABSTRACT FROM AUTHOR]

Inflammatory cytokines released by synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine‐mediated pathological communication between the synovium and cartilage. Cartilage‐specific network analysis of injured young and aged murine knees revealed aberrant matrix remodeling as a transcriptomic response unique to aged knees displaying accelerated cartilage degradation. Next, network‐based cytokine inference with pharmacological manipulation uncovered IL6 family member, Oncostatin M (OSM), as a driver of the aberrant matrix remodeling. By implementing a phenotypic drug discovery approach, we identified that the activation of OSM recapitulated an "inflammatory" phenotype of knee osteoarthritis and highlighted high‐value targets for drug development and repurposing. These findings offer translational opportunities targeting the inflammation‐driven osteoarthritis phenotype. [ABSTRACT FROM AUTHOR]

Key points Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro‐adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed Pgc‐1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated in silico and in situ approaches to induce Pgc‐1α overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the Pgc‐1α–mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age‐related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations. Fat accumulation is a quintessential feature of aged skeletal muscle. While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined. This study implemented a series of network medicine approaches and uncovered Pgc‐1α as a mechanistic driver of the regulation of fibro‐adipogenic progenitors (FAPs) by physical activity. Integrated in silico and in situ approaches to induce Pgc‐1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of Pgc‐1α‐mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case highlights the biomechanical influence of toe amputation on contralateral limb force elevation, possibly through reduced ipsilateral plantar flexor torque production. These findings provide insight into toe amputation‐related compensatory gait mechanics with greater inter‐limb asymmetry, which may increase the risk of musculoskeletal comorbidities, including osteoarthritis in contralateral limb. [ABSTRACT FROM AUTHOR]

Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the majority of clinically presenting KOA, the bulk of our mechanistic understanding of KOA has been derived using surgically induced posttraumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics data analysis to elucidate pathogenic mechanisms of age-related KOA in mice. Protein-level data were integrated with transcriptomic profiling to reveal inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of cartilage aging were unique from those observed following PTOA, with less than 3% overlap between the 2 models. At the nexus of the 3 aging hallmarks, advanced glycation end product (AGE)/receptor for AGE (RAGE) emerged as the most statistically robust pathway associated with age-related KOA. This pathway was further supported by analysis of mass spectrometry data. Notably, the change in AGE-RAGE signaling over time was exclusively observed in male mice, suggesting sexual dimorphism in the pathogenesis of age-induced KOA in murine models. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a sex-dependent driver of age-related KOA. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is a leading cause of knee pain and disability due to irreversible cartilage degeneration. Previous studies have not identified modifiable risk factors for KOA. In this preliminary cross-sectional study, we aimed to test the following hypotheses: individuals with severe KOA would have a significantly lower quadriceps rate of force development (RFD) than individuals with early KOA, and the decrease in quadriceps RFD would be greater than the decrease in maximum quadriceps strength in individuals with severe KOA. The maximum isometric strength of the quadriceps was assessed in individuals with mild (Kellgren and Lawrence [K&L] grade 1–2) and severe KOA (K&L grade 3–4) using a handheld dynamometer. The RFD was analyzed at 200 ms from torque onset and normalized to the body mass and maximum voluntary isometric contraction torque. To test whether the quadriceps RFD was lowered and whether the lower in the quadriceps RFD was greater than the lower in maximum quadriceps strength in individuals with severe knee OA, the Mann–Whitney U-test and analysis of covariance were performed, respectively. The effect size (ES) based on Hedges' g with a 95% confidence interval (CI) was calculated for the quadriceps RFD and maximum quadriceps strength. Sixty-six participants were analyzed. Individuals with severe KOA displayed significantly lower quadriceps RFD (p = 0.009), the lower being greater than the lower in maximum quadriceps strength (between-group difference, ES: 0.88, -1.07 vs. 0.06, -0.22). Our results suggest that a decreased quadriceps RFD is a modifiable risk factor for progressive KOA. Our finding could help in the early detection and prevention of severe KOA. [ABSTRACT FROM AUTHOR]

Objective: Knee osteoarthritis (OA) has been suggested to increase the risk of falls. Low back pain (LBP) is a potential risk factor for falls in people with knee OA, but this issue has not been addressed adequately in previous studies. The objective of this study was to investigate the relationship between LBP and falls in people with knee OA in a 12‐month period. Methods: Participants with knee OA (Kellgren/Lawrence [K/L] grade ≥1) completed questionnaires for LBP and falls that occurred in the preceding 12 months. Binary and ordinal logistic regression analyses were performed to assess the relationship between LBP or moderate‐to‐severe LBP (numeric rating scale ≥4 points) and any fall (≥1 fall) or recurrent falls (≥2 falls) after adjustment for age, sex, K/L grade, knee pain severity, and quadriceps strength. Sensitivity analyses were performed excluding people with sciatica, nonchronic LBP, K/L grade 1, and those receiving pain medications. Results: We included 189 participants (ages 61–90 years, 78.3% women) in this study. Of these participants, 41 (21.6%) reported falls in the preceding 12 months. People with any LBP (n = 101) and those with moderate‐to‐severe LBP (n = 45) had 2.7‐ and 3.7‐times higher odds of recurrent falls, respectively. Sensitivity analyses revealed a strong correlation between moderate‐to‐severe LBP and recurrent falls. Conclusion: Thorough investigation of LBP as a risk factor for recurrent falls in people with knee OA may provide a novel insight into the pathomechanics of recurrent falls in this population. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that varus thrust visualized during gait is associated with a higher prevalence of low back pain (LBP) in individuals with knee osteoarthritis (OA).Methods: Individuals with knee OA (Kellgren/Lawrence grade ≥1) underwent a gait observation to assess varus thrust. The participants identified LBP and its severity using questionnaires. Logistic regression analyses were performed to examine the association between varus thrust and LBP.Results: We included 205 participants (mean age 68.19 years; 72.20% women). A total of 45 participants (22.0%) showed varus thrust in their painful knee, in whom 31 (68.89%) and 18 (40.00%) were identified as having any LBP and moderate-to-severe LBP (numerical rating scale ≥4 points), respectively. Patients with varus thrust demonstrated a 3.6-fold higher risk of the presence of moderate-to-severe LBP (95% confidence interval [95% CI] 1.62-8.10). In patients with LBP, the presence of varus thrust was associated with more severe LBP intensity (proportional odds ratio 2.25 [95% CI 1.02-4.96]).Conclusion: This study highlights the novel relationship between varus thrust and LBP, which supports the idea of a biomechanical link, the so-called knee-spine syndrome. These findings provide new insight for clarifying the pathogenesis of LBP related to knee OA. [ABSTRACT FROM AUTHOR]

Background: Postmenopausal women are at risk of fall and fracture with the physical decline. Distal radius fracture (DRF) is considered as the primary fragility fracture, and women with this fracture showed poor results in the usual Timed Up-and-Go (TUG) test, indicating a decline in balance and physical ability. The detailed physical characteristics of female DRF patients have not been extensively examined.Research Question: Is the novel laser TUG system able to detect and analyze the detailed gait characteristics in patients with DRF whose physical ability has tended to decline?Methods: In this cross-sectional case control study, the gait characteristics of 32 female patients　with DRF who had undergone surgery were evaluated at 2 weeks postoperatively with a　laser TUG system to analyze the detailed leg motion during normal TUG test.　Forty-three age- and sex-matched non-fractured women were evaluated by the laser TUG system as controls. Lifestyle and present illness were corrected at the time of TUG measurement. Detailed data during laser TUG in both groups were compared statistically, and odds ratio and thread shod of the fracture was elucidated through a　logistic regression analysis.Results: DRF patients showed slower speed and had to do more steps to complete the TUG test. Furthermore, asymmetric trajectory and significantly further distance from the marker were observed. Thirteen steps to complete the TUG test was the thread shod of DRF.Significance: Detailed gait characteristics of patients with DRF were detected by the laser TUG system. The gait decline and abnormality could be one of the reasons of consecutive fragility fracture. To prevent secondary fragility fractures, this system can be useful for screening. [ABSTRACT FROM AUTHOR]