Osteoarthritis (OA) is the most prevalent disorder of synovial joint affecting multiple joints. In the past decade, we have witnessed conceptual switch of OA pathogenesis from a ‘wear and tear’ disease to a disease affecting entire joint. Extensive studies have been conducted to understand the underlying mechanisms of OA using genetic mouse models and ex vivo joint tissues derived from individuals with OA. These studies revealed that multiple signalling pathways are involved in OA development, including the canonical Wnt/β‐catenin signalling and its interaction with other signalling pathways, such as transforming growth factor β (TGF‐β), bone morphogenic protein (BMP), Indian Hedgehog (Ihh), nuclear factor κB (NF‐κB), fibroblast growth factor (FGF), and Notch. The identification of signalling interaction and underlying mechanisms are currently underway and the specific molecule(s) and key signalling pathway(s) playing a decisive role in OA development need to be evaluated. This review will focus on recent progresses in understanding of the critical role of Wnt/β‐catenin signalling in OA pathogenesis and interaction of β‐catenin with other pathways, such as TGF‐β, BMP, Notch, Ihh, NF‐κB, and FGF. Understanding of these novel insights into the interaction of β‐catenin with other pathways and its integration into a complex gene regulatory network during OA development will help us identify the key signalling pathway of OA pathogenesis leading to the discovery of novel therapeutic strategies for OA intervention.

Background: High-intensity interval training (HIIT) reportedly improves bone metabolism and increases bone mineral density (BMD). The purpose of the present study was to investigate whether lactate mediates the beneficial effects of exercise on BMD, bone microarchitecture, and biomechanical properties in an established osteoporotic animal model. In addition, we hypothesized that lactate-induced bone augmentation is achieved through enhanced osteoblast differentiation and mineralization. Methods: A total of 50 female C57BL/6 mice were randomly allocated into 5 groups: the nonovariectomized group, the ovariectomized group (OVX), the HIIT group (OVX + HIIT), the HIIT with lactate transporter inhibition group (OVX + HIIT + INH), and the lactate subcutaneous injection group (OVX + LAC). After 7 weeks of intervention, bone mass, bone strength, and bone formation/resorption processes were evaluated via microcomputed tomography (micro-CT), biomechanical testing, histological analysis, and serum biochemical assays; in vitro studies were performed to explore the bone anabolic effect of lactate at the cellular level. Results: Micro-CT revealed significantly increased BMD in both the OVX + HIIT group (mean difference, 41.03 mg hydroxyapatite [HA]/cm³ [95% CI, 2.51 to 79.54 mg HA/cm³]; p = 0.029) and the OVX + LAC group (mean difference, 40.40 mg HA/cm³ [95% CI, 4.08 to 76.71 mg HA/cm³]; p = 0.031) compared with the OVX group. Biomechanical testing demonstrated significantly improved mechanical properties in those 2 groups. However, the beneficial effects of exercise on bone microstructure and biomechanics were largely abolished by blocking the lactate transporter. Notably, histological and biochemical results indicated that increased bone formation was responsible for the bone augmentation effects of HIIT and lactate. Cell culture studies showed a marked increase in the expression of osteoblastic markers with lactate treatment, which could be eliminated by blocking the lactate transporter. Conclusions: Lactate may have mediated the bone anabolic effect of HIIT in osteoporotic mice, which may have resulted from enhanced osteoblast differentiation and mineralization. Clinical Relevance: Lactate may mediate the bone anabolic effect of HIIT and serve as a potential inexpensive therapeutic strategy for bone augmentation.

Background: Thoracolumbar burst fractures are a common traumatic vertebral fracture in the spine, and pedicle screw fixation has been widely performed as a safe and effective procedure. However, after the stabilization of the thoracolumbar burst fractures, whether or not to remove the pedicle screw implant remains controversial. This review aimed to assess the benefits and risks of pedicle screw instrument removal after fixation of thoracolumbar burst fractures. Methods: Data sources, including PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Clinical trials.gov, were comprehensively searched. All types of human studies that reported the benefits and risks of implant removal after thoracolumbar burst fractures, were selected for inclusion. Clinical outcomes after implant removal were collected for further evaluation. Results: A total of 4051 papers were retrieved, of which 35 studies were eligible for inclusion in the review, including four case reports, four case series, and 27 observational studies. The possible risks of pedicle screw removal after fixation of thoracolumbar burst fractures include the progression of the kyphotic deformity and surgical complications (e.g., surgical site infection, neurovascular injury, worsening pain, revision surgery), while the potential benefits of pedicle screw removal mainly include improved segmental range of motion and alleviated pain and disability. Therefore, the potential benefits and possible risks should be weighed to support patient-specific clinical decision-making about the removal of pedicle screws after the successful fusion of thoracolumbar burst fractures. Conclusions: There was conflicting evidence regarding the benefits and harms of implant removal after successful fixation of thoracolumbar burst fractures, and the current literature does not support the general recommendation for removal of the pedicle screw instruments, which may expose the patients to unnecessary complications and costs. Both surgeons and patients should be aware of the indications and have appropriate expectations of the benefits and risks of implant removal. The decision to remove the implant or not should be made individually and cautiously by the surgeon in consultation with the patient. Further studies are warranted to clarify this issue. Level of evidence: level 1.

Osteoarthritis is a leading degenerative disease worldwide that significantly impairs physical function and quality of life. With an ageing population, the epidemiological burden of osteoarthritis is expected to intensify, making systematic analysis and trend prediction essential for refining treatment and prevention strategies. Data from the 2021 Global Burden of Disease database was employed to analyse trends in the incidence, prevalence, and disability-adjusted life years of osteoarthritis from 1990 to 2021. This research spans global, regional, and national perspectives, aiming to guide future health interventions. By 2021, the number of patients affected by osteoarthritis had reached 607 million, with predictions estimating a rise to 765 million by 2060. There is a positive correlation between Social Development Index and osteoarthritis burden, illustrating that higher incidence and prevalence rates are associated with greater economic development. East Asia currently leads with the highest count of osteoarthritis cases, whereas Oceania has the fewest. Osteoarthritis incidence is climbing across all adult age groups, with women consistently exhibiting higher rates than men at every age. High body mass Index stands as the most significant risk factor for the condition. The total number of osteoarthritis cases is expected to keep rising, underscoring the ongoing challenge in managing this pervasive disease. Osteoarthritis persists as a substantial global health challenge, exhibiting a continuous upward trend from 1990 to 2021. This study provides critical insights for public health policy-making and resource allocation, supporting future interventions and disease control efforts.

Although bone morphogenetic protein 2 (BMP2) can induce chondrogenic differentiation of mesenchymal stem cells (MSCs), its induction of endochondral ossification limits the application of BMP2-based cartilage regeneration. Here, we clarified the mechanisms of BMP2-induced endochondral ossification of MSCs. In vitro and in vivo chondrogenic, osteogenic, and angiogenic differentiation models of MSCs were constructed. The expression of target genes was identified at both protein and mRNA levels. RNA sequencing, molecular docking, co-immunoprecipitation, and chromatin immunoprecipitation followed by sequencing were applied to investigate the molecular mechanisms. We found that BMP2 up-regulated the expression of Notch receptors and ligands in MSCs. Notch1 signaling activation was related to inhibition of chondrogenic differentiation, promotion of osteogenic and angiogenic differentiation. In vivo ectopic stem cell implantation identified that Notch1 signaling activation blocked BMP2-induced chondrogenesis and facilitated endochondral ossification of MSCs. Mechanistically, we elucidated Notch1 intracellular domain (NICD1)-RBPjk complex binding to SRY-box transcription factor 9 (Sox9) and vascular endothelial growth factor A (VEGFA) promoters to decrease Sox9 expression and increase VEGFA expression. These findings suggest that Notch1 signaling can regulate BMP2-induced endochondral ossification by promoting RBPjk-mediated Sox9 inactivation and VEGFA expression. It is conceivable that targeting Notch1 signaling mediated endochondral ossification would benefit BMP2-based cartilage regeneration.

Lactylation, a recently discovered histone and non-histone modification driven by lactate, has redefined the understanding of how metabolic by-products regulate gene expression. Beyond its conventional role as an energy substrate, lactate emerges as a pivotal signaling mediator that couples cellular metabolism with epigenetic regulation. In musculoskeletal disorders, aberrant lactylation has been implicated in the disruption of osteogenic-osteoclastic balance, extracellular matrix homeostasis, and regenerative capacity, thereby linking cellular metabolic stress to pathological tissue remodeling. These findings position lactylation as a unifying mechanism across osteoporosis, osteoarthritis, intervertebral disc degeneration, and sarcopenia. Yet, the field remains in its infancy: the enzymatic machinery of lactylation is incompletely characterized, context-specific functions are poorly defined, and translation to human pathology is scarce. Conceptualizing lactylation as a metabolic-epigenetic nexus not only reframes our understanding of musculoskeletal biology but also highlights new opportunities for biomarker discovery and targeted epigenetic therapies. Addressing these challenges will be essential to harness the clinical potential of this emerging regulatory paradigm.