Tendinopathy is a prevalent aging-related disorder characterized by pain, swelling, and impaired function, often resulting from micro-scarring and degeneration caused by overuse or trauma. Current interventions for tendinopathy have limited efficacy, highlighting the need for innovative therapies. Mitochondria play an underappreciated and yet crucial role in tenocytes function, including energy production, redox homeostasis, autophagy, and calcium regulation. Abnormalities in mitochondrial function may lead to cellular senescence. Within this context, this review provides an overview of the physiological functions of mitochondria in tendons and presents current insights into mitochondrial dysfunction in tendinopathy. It also proposes potential therapeutic strategies that focus on targeting mitochondrial health in tenocytes. These strategies include: (1) utilizing reactive oxygen species (ROS) scavengers to mitigate the detrimental effects of aberrant mitochondria, (2) employing mitochondria-protecting agents to reduce the production of dysfunctional mitochondria, and (3) supplementing with exogenous normal mitochondria. In conclusion, mitochondria-targeted therapies hold great promise for restoring mitochondrial function and improving outcomes in patients with tendinopathy. : Tendinopathy is challenging to treat effectively due to its poorly understood pathogenesis. This review thoroughly analyzes the role of mitochondria in tenocytes and proposes potential strategies for the mitochondrial treatment of tendinopathy. These findings establish a theoretical basis for future research and the clinical translation of mitochondrial therapy for tendinopathy.

Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment.

Intervertebral disc degeneration(IVDD) is the primary etiology of low back pain and radicular pain. Recent studies have found that chemokines play a role in IVDD, but the underlying mechanism is largely unclear.

Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown.

Repair of long bone defects remains a major challenge in clinical practice, necessitating the use of bone grafts, growth factors, and mechanical stability. Hence, a combination therapy involving a 3D-printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) scaffold coated with polydopamine (PDA) and alginate microbeads (AM) for sustained delivery of bone morphogenetic protein-2 (BMP-2) was investigated to treat long bone segmental defects.

Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. However, there is currently no effective treatment for SOP. The Zhuangyao Jianshen Wan (ZYJSW) pill is traditionally believed to possess kidney-nourishing and bone-strengthening effects, demonstrating efficacy in treating fractures. Despite this, its effectiveness and mechanism in SOP remain unclear. This study aims to investigate the therapeutic potential of ZYJSW in treating SOP in senescence accelerated mouse prone 6 (SAMP6, P6) mice, and elucidate the underlying mechanisms.

Injectable hydrogels are widely used in drug delivery and the repair of irregular tissue defects due to their advantages such as convenient and minimally invasive operation. Although the existing injectable hydrogels have excellent biocompatibility and osteoconduction, they still face clinical challenges such as low osteogenic activity. The key requirements for improved injectable hydrogels as repair materials for non-load bearing bone defects are optimal handling properties, the ability to fill irregular defects and provide osteoinductive stimulation.

Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss.

Exosomes produced by mesenchymal stem cells (MSCs) have vascular generative properties and are considered new effective candidates for the treatment of bone defects as alternatives to cell therapy. Improving the pro-regenerative function and efficacy of exosomes has been a popular research topic in the field of orthopaedics.

Neuroinflammation plays a crucial role in the repair of spinal cord injury (SCI), with microglia, pivotal in neuroinflammation, driving either degeneration or recovery in this pathological process. Recently, plasma-derived exosomes (denoted Exos) have presented a high capacity for promoting functional recovery of SCI through the anti-inflammatory effects, and pretreated exosomes are associated with better outcomes. Thus, we aimed to explore whether melatonin-pretreated plasma-derived exosomes (denoted MExo) could exert superior effects on SCI, and attempted to elucidate the potential mechanisms.

As the population aging progresses, age-related osteoporosis has become one of the most common and severe chronic degenerative diseases. Due to insufficient understanding of its complex pathomechanisms, current clinical treatments often suffer from many negative effects. Type H vessels play critical role in bone remodeling owing to their specialized function in coupling angiogenesis and osteogenesis. Increasing evidences have shown a close association between the age-related decline of type H vessels and bone loss. However, the underlying mechanisms whereby the regression of type H vessels with aging remain largely unknown.

Displaced fragility fractures of the pelvis (FFP) pose significant challenges in orthopaedic trauma, owing to patient comorbidities, deteriorating bone quality, and surgical complexities. Despite technological advancements, no robotic methods have been documented for displaced FFP management. To address this, we introduced an advanced robot-assisted fracture reduction system, comprising a tracking device, path planning software, and robotic arms. This study evaluated fifteen consecutive patients with displaced FFP (average age 80.4 ± 9.1 years), who underwent robot-assisted reduction and internal fixation (RARIF) between January 2022 and May 2023. All were categorized as Rommens FFP type III, with a median time of 6 days (range 4-11) from injury to surgery. Operative times averaged 165 ± 44 min, with median blood loss of 50 mL. Postoperative radiographs showed all patients achieved excellent or good reductions as per Matta criteria, marking a 100 % success rate. A 6-month follow-up revealed an average modified Majeed score of 81.4, with 85.7 % of patients rated excellent or good. All fractures healed without complications. Leveraging our intelligent system, RARIF proves to be a safe and effective approach for displaced FFP, facilitating postoperative pain alleviation and early mobilization despite compromised health and bone conditions. This approach may revolutionize the management of FFP in an increasingly aging population, signaling a significant shift in therapeutic strategies. Translational Potential of this Article: Elderly patients with displaced FFP often present complex surgical challenges due to comorbidities and poor bone quality, complicating reduction procedures and often leading to ineffective fixation. Addressing these challenges, we have developed an innovative robot-assisted fracture reduction system, offering a practical alternative to conventional methods. This system optimizes the applied force and direction during the reduction process, thereby reducing the needs for manual and repetitive attempts. Our report, detailing the successful implementation of this technique in 15 FFP cases, signifies a considerable leap forward in the field of orthopaedic surgery. This technique notably benefits the elderly population, a group traditionally marginalized in receiving care for complex orthopedic conditions.

In recent years, many countries have actively implemented programs and strategies to promote physical education and sports. Despite these efforts, the increase in physical activity has been accompanied by a significant rise in muscle and tendon-ligament injuries, with Achilles tendon rupture being the most prevalent, accounting for 47 % of such injuries. This review aims to summarize all significant factors determining the predisposition of the Achilles tendon to rupture, to develop effective personalized prevention measures.

Cell polarity refers to the orientation of tissue and organelles within a cell and the direction of its function. It is one of the most critical characteristics of metazoans. The development, growth, and functional tissue distribution are closely related to holistic tissue or organ homeostasis. However, the connection between cell polarity and osteoarthritis (OA) is less well-known. In OA, multiple chondrocyte clusters and tissue disorganisation can be observed in the degraded cartilage tissue. The excessive upregulation of the planar cell polarity (PCP) signalling pathway leads to the loss of cell polarity and organisation in OA progression and aetiology. Recent research has become increasingly aware of the importance of cell polarity and its correlation with OA. Several cell polarity-related treatments have shed light on OA. A thorough understanding of cell polarity and OA would provide more insights for future investigations to treat this worldwide disease.

Chondrocyte hypertrophy is a potential target for osteoarthritis (OA) treatment, with Indian hedgehog (IHH), glioma-associated oncogene homolog (GLI), and hypoxia-inducible factor-2α (HIF-2α) being closely associated with chondrocyte hypertrophy during OA progression. Whereas IHH can modulate chondrocyte hypertrophy, interference with IHH signalling has not achieved the anticipated therapeutic effects and poses safety concerns, necessitating further clarification of the specific mechanisms by which IHH affects articular cartilage degeneration. Inhibition of the HIF-2α overexpression in cartilage slows the progression of early OA, but the mechanisms underlying HIF-2α accumulation in OA cartilage remain unclear. The aim of this study was to determine the function of Ihh, as well as its downstream factors, in chondrocytes, based on an early osteoarthritis (OA) mouse model and in vitro chondrocyte model.

Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic investigations using various transgenic mice. The current study reports the development of a reproducible murine DO model.

Intervertebral disc degeneration (IVDD) is widely recognized as one of the leading causes of low back pain. Intervertebral disc cells are the main components of the intervertebral disc (IVD), and their functions include synthesizing and secreting collagen and proteoglycans to maintain the structural and functional stability of the IVD. In addition, IVD cells are involved in several physiological processes. They help maintain nutrient metabolism balance in the IVD. They also have antioxidant and anti-inflammatory effects. Because of these roles, IVD cells are crucial in IVDD. When IVD cells are subjected to oxidative stress, mitochondria may become damaged, affecting normal cell function and accelerating degenerative changes. Mitochondria are the energy source of the cell and regulate important intracellular processes. As a key site for redox reactions, excessive oxidative stress and reactive oxygen species can damage mitochondria, leading to inflammation, DNA damage, and apoptosis, thus accelerating disc degeneration.

Active vitamin D insufficiency accelerates the development of osteoporosis, with senescent bone cells and the senescence-associated secretory phenotype (SASP) playing crucial roles. This study aimed to investigate whether the senolytic agent ABT263 could correct osteoporosis caused by active vitamin D insufficiency by selectively clearing senescent cells.

The repair of bone defects has always been a significant challenge in clinical medicine. To address this challenge, doctors often utilize autologous bone grafts, allogeneic bone grafts and artificial bone substitutes. However, the former two methods may result in additional trauma and complications, while allogeneic bone grafts carry the risks of immune rejection and disease transmission. Magnesium phosphate cement (MPC), as a artificial bone substitutes, has been a potential biomaterial for repairing bone defects, but its clinical application is limited by insufficient mechanical strength and poor osteoinductive activity.

Muscle atrophy or sarcopenia is the loss of muscle mass and strength and leads to an increased risk of disability and death including osteoporotic fractures. Currently, there are no available clinical biologic agents for the treatment of sarcopenia. Since exosomes have become increasingly attractive as a novel therapeutic approach due to their ability to facilitate cell-cell transfer of proteins and RNAs, promoting cell repair and function recovery, we hypothesized that human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) might benefit muscle atrophy in age-related and dexamethasone-induced sarcopenia animal models.

Heterotopic ossification (HO) refers to the abnormal development of bone in soft tissue rather than within bone itself. Previous research has shown that sensory nerve prostaglandin E2 receptor 4 (EP4) signaling not only governs pain perception but also influences bone formation. However, the relationship between sensory nerve EP4 and the pathogenesis of HO in the Achilles tendon remains unclear. This study aims to investigate this relationship and the underlying mechanisms.