Siyi Liu

Aims: A strong correlation has been observed between diabetes mellitus (DM) with the pathogenesis of osteoarthritis (OA). This study aimed to elucidate the cellular and molecular mechanisms by which DM exacerbates OA, through multiomics analysis of synovium and cartilage from OA patients with type 2 DM (T2DMOA). Methods: Single-cell RNA sequencing, bulk RNA sequencing, and metabolome profiling were performed on knee cartilage and synovium from 21 patients with OA or T2DMOA to investigate the differences in transcriptional landscape, intercellular signalling networks, transcription factor regulatory patterns, and alterations in metabolic pathways. Results: Single-cell profiling of synovium-cartilage tissues revealed distinct pathological alterations in T2DMOA patients compared to non-diabetic OA controls. In the T2DMOA synovium, we observed significantly enhanced differentiation of sublining fibroblasts into lining fibroblasts, along with enriched pathways governing energy metabolism, vasculogenesis, and cell proliferation. For cell-cell communication between cartilage and synovium, hepatocyte growth factor ( HGF )-mesenchymal-epithelial transition factor ( MET ), fibroblast growth factors ( FGF ) 10-FGF receptor 1 ( FGFR1 ), and nicotinamide phosphoribosyl transferase ( NAMPT )-(integrin subunit alpha 5 ( ITGA5 ) + integrin subunit beta 1 ( ITGB1 )) from synoviocytes to chondrocytes, as well as angiopoietin-like protein 2 ( ANGPTL2 )-toll-like receptor 4 ( TLR4 ) and ANGPTL2- ( ITGA5 + IGTB1 ) from chondrocytes to synoviocytes, showed a notable increase in T2DMOA patients. Conversely, T2DMOA cartilage exhibited a pronounced suppression of metabolic activity, particularly in amino acid transport and glycan biosynthesis. Additionally, transcription factors of synoviocytes and chondrocytes were clustered into five and four major modules, respectively, with various functions. Conclusion: Our findings define a diabetes-specific OA phenotype, characterized by aberrant synovial fibroblast activation, dysregulated synovium-cartilage crosstalk, and impaired cartilage metabolism. This integrated view establishes T2DMOA as a unique metabolic-subtype of OA, driven by disrupted intercellular communication and metabolic reprogramming. Cite this article: Bone Joint Res 2026;15(6):584–600.

Aims: Osteoarthritis (OA) is a common degenerative disease that leads to pain, disability, and reduced quality of life. Orientin exhibits considerable anti-inflammatory and antioxidative properties, but its role in chondrocyte senescence and OA progress has not yet been fully characterized. The aim of this study was to evaluate the protective effects of orientin on OA.Methods: The role of orientin in extracellular matrix (ECM) degradation, mitochondrial homeostasis, and chondrocyte senescence was investigated in vitro. Meanwhile, we used molecular docking, small molecular inhibitors, and RNA interference to screen and validate candidate proteins regulated by orientin. In an anterior cruciate ligament transection (ACLT) rat model, radiograph, micro-CT, and various histological examinations were applied to evaluate the therapeutic effects of orientin on OA.Results: We found that orientin inhibited ECM degradation and senescence-associated secretory phenotype (SASP) factor expression in interleukin (IL)-1β-treated chondrocytes. Additionally, orientin reduced the level of reactive oxygen species (ROS) and improved mitochondrial homeostasis. Furthermore, orientin suppressed IL-1β-induced activation of the nuclear factor kappa B (NF-κB) signalling pathway. We also found that orientin bound to phosphoinositide 3-kinase (PI3K) and inhibited NF-κB cascades via the PI3K/AKT pathway. In vivo, we demonstrated that orientin improved cartilage wear and reduced synovial inflammation and osteophyte in an ACLT rat model.Conclusion: Orientin improves mitochondrial homeostasis, inhibits chondrocyte senescence, and alleviates OA progress via the PI3K/AKT/NF-κB axis, which suggests that orientin is a potential effective therapeutic agent for OA.Cite this article: Bone Joint Res 2025;14(3):245–258.

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Our study aimed to explore the protective effects of DEN on OA both in vitro and in vivo. We found that DEN inhibited extracellular matrix (ECM) degradation and promoted ECM synthesis. Meanwhile, DEN inhibited senescence-associated secretory phenotype (SASP) factors expression and senescence phenotype in IL-1β-treated chondrocytes. Furthermore, DEN improved mitochondrial function and reduced the production of intracellular reactive oxygen species (ROS). Also, DEN suppressed IL-1β-induced activation of the NF-κB pathway. Further, using NAC (ROS inhibitor), we found that DEN might inhibit NF-κB cascades by reducing ROS. Additionally, X-ray, micro-CT, and histological analyses in vivo demonstrated that DEN significantly alleviated cartilage inflammation, ECM degradation, and subchondral alterations in OA progression. In conclusion, DEN inhibits SASP factors expression and senescence phenotype in chondrocytes and alleviated the progression of OA via the ROS/NF-κB axis, which provides innovative strategies for the treatment of OA.

Objective To present the use of an intermediate dorsal neurocutaneous flap for the reconstruction of defects on the distal foot. Methods From September 2016 to October 2018, five patients (mean age at operation 33.8 years; range, 7–70 years; female/male = 2/3) with skin defects on one of their feet caused by road‐traffic accidents, electrical injury, and syndactyly correction were retrospectively reviewed. The size of the defects ranged from 2.0 cm × 1.0 cm to 5.0 cm × 3.5 cm. All patients had undergone a reconstruction surgery using intermediate dorsal neurocutaneous flap. One patient underwent a syndactyly correction, and four patients first experienced aggressive debridement. The sizes of the flaps were between 5.0 cm × 2.0 cm and 6.0 cm × 4.0 cm. The function, appearance, and pain of the injured foot were assessed using the Chinese Manchester Foot Pain and Disability Index and visual analogue scale. Results These five patients were systematically followed up for a mean of 15.8 months (range, 12–20 months). The donor sites were closed primarily in two cases, and skin grafts were performed in three cases. All the flaps survived with a success rate of 100%; the wounds healed well, and the color matches were excellent. Partial superficial flap necrosis occurred in one of five flaps, which was treated by dressing change using a hypertonic saline gauze. No significant problems were found at the donor site in any patient immediately afterwards or at follow‐up. There were no problems in any patients associated with wearing shoes. Based on the Chinese Manchester Foot Pain and Disability Index, four patients were strongly satisfied and one was satisfied with the recovery of physical function; all the patients were strongly satisfied with the appearance of the injured foot; all five patients had an excellent score of pain intensity subscale. Except for one patient who reported mild pain, all the other patients reported no pain based on the visual analogue scale. Two typical cases are presented in this paper. Conclusions The intermediate dorsal neurocutaneous flap is an alternative and effective technique that can reliably cover minor‐ to medium‐sized defects on the distal foot, toes, and web spaces. This surgical method leads to satisfactory functional recovery with minimal donor site morbidity, and no major vessels need to be sacrificed. This procedure offers an advisable option for orthopaedic surgeons to treat defects on the distal foot.

The use of fibular graft for the reconstruction of bone defects has been demonstrated to be a reliable method. The aim of this study was to assess the clinical outcome of graft union, functional outcome (hypertrophy of the graft bones) and complications of both non-vascularized and vascularized grafts. From 1981 to 2015, 10 patients were treated using non-vascularized fibular graft or free vascularized fibular graft. The outcomes were bony union time, graft hypertrophy and complications based on radiograph and functional outcomes according to the Musculoskeletal Tumor Society (MSTS) score. Mobility of the ankle at the donor site was evaluated using the Kofoed ankle score system. This study included 10 patients with an average follow-up of 6.8 years. The union rate for all patients was 100%. The mean union time was 21.3 weeks for vascularized fibular grafts and 30.5 weeks for non-vascularized fibular grafts (P = .310). There was a significant difference between the upper limbs and the lower limbs regarding hypertrophy of the grafts in 5 patients (P = .003). The mean MSTS score in 10 patients was 84% (range 53%–97%). Stress fracture of the graft occurred in 1 patient. Donor site complications, including valgus deformity and length discrepancy, between 2 legs occurred in 2 patients who were under 18 years of age at the time of operation (P = .114). The mean Kofoed score was 96.8 (range 88–100). A greater increase in hypertrophy of grafts was observed with reconstruction in the lower limbs. There was no difference in MSTS score between these 2 types of grafts. Children were more likely to experience the valgus deformity at the donor site after harvesting the fibula. Keeping at least the distal 1/4 of the fibula intact during the surgery is a valid means of ensuring ankle stability at the donor site, and children should be considered for prophylactic distal tibiofibular synostosis creation to prevent the valgus deformity of the ankle at the donor site.