Exostoses

To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.

Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1Col2a1Cre), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1Col2a1Cre animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1Col2a1Cre mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

ObjectivesPrior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of Sirt6 deficiency on the development of post-traumatic and age-associated OA in mice.MethodsMale cartilage-specific Sirt6-deficient mice and Sirt6 intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting.ResultsSirt6-deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that SIRT6 depletion significantly repressed cartilage extracellular matrix (eg, COL2A1) and anabolic growth factor (eg, insulin-like growth factor-1 (IGF-1)) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced SIRT6 activation promoted IGF-1 signalling by increasing Aktser473 phosphorylation.ConclusionsSIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA.

BackgroundHereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder frequently associated with progressive forearm deformities, including ulnar shortening, radial bowing, and radial head dislocation. Ulnar lengthening using distraction osteogenesis has become the principal surgical strategy; however, outcomes, techniques, and complication profiles vary across studies. This systematic review and meta-analysis synthesize contemporary evidence on radiographic correction, functional outcomes, and complications following ulnar lengthening for HME-related forearm deformities.MethodsA systematic search of SciSpace, PubMed, and Google Scholar was performed to identify studies published between January 2015 and December 2025 evaluating ulnar lengthening in patients with HME. Observational studies reporting radiographic, functional, or complication outcomes were included. Data were extracted on patient characteristics, surgical techniques, radiographic parameters, functional outcomes, and complications. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses were conducted, with heterogeneity assessed using the I2 statistic.ResultsThirty observational studies comprising 350 patients and 380 forearms were included, with a mean follow-up of 38.6 months. The pooled mean ulnar lengthening achieved was 33.8 mm (95% CI: 28.4-39.2; I2 = 68%). Significant improvements were observed in radial articular angle (mean difference - 6.3°, 95% CI: - 8.7 to - 3.9; I2 = 52%) and ulnar variance (mean difference - 15.4 mm, 95% CI: - 18.2 to - 12.6; I2 = 58%). Radial head reduction was achieved in 76% of affected forearms. Functional outcomes improved significantly, with DASH scores decreasing by a pooled mean of 12.7 points (p ConclusionsUlnar lengthening via distraction osteogenesis provides effective radiographic correction and meaningful functional improvement in patients with HME-related forearm deformities, with acceptable complication rates. Monolateral external fixation is the most commonly employed technique and yields reliable outcomes. Despite encouraging results, the evidence base is limited to observational studies with heterogeneous reporting, underscoring the need for prospective studies with standardized outcome measures and longer follow-up.