The involvement of chondrocyte ferroptosis in the development of osteoarthritis (OA) has been observed, and Sarsasapogenin (Sar) has therapeutic promise in a variety of inflammatory diseases. This study investigates the potential influence of Sar on the mechanism of chondrocyte ferroptotic cell death in the progression of osteoarthritic cartilage degradation. An in vivo medial meniscus destabilization (DMM)-induced OA animal model as well as an in vitro examination of chondrocytes in an OA microenvironment induced by interleukin-1β (IL-1β) exposure were employed. Histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability, and Micro-CT analysis were utilized in conjunction with gene overexpression and knockdown to evaluate the chondroprotective effects of Sar in OA progression and the role of Yes-associated protein 1 (YAP1) in Sar-induced ferroptosis resistance of chondrocytes. In this study we found Sar reduced chondrocyte ferroptosis and OA progression. And Sar-induced chondrocyte ferroptosis resistance was mediated by YAP1. Furthermore, infection of siRNA specific to YAP1 in chondrocytes reduced Sar's chondroprotective and ferroptosis-suppressing effects during OA development. The findings suggest that Sar mitigates the progression of osteoarthritis by decreasing the sensitivity of chondrocytes to ferroptosis through the promotion of YAP1, indicating that Sar has the potential to serve as a therapeutic approach for diseases associated with ferroptosis.

In clinical practice, repairing osteochondral defects (OCDs) is challenging because of the complex cartilage/subchondral bone structure and intricate immunological microenvironment. Here, we identify the crucial role of adaptive immunity dysfunction by revealing that an increase of T helper 17 (Th17) cells exacerbated osteochondral tissue degradation via its pro-inflammatory cytokine interleukin-17 (IL-17) in the early-stage OCDs. Next, we leveraged this adaptive immunity mechanism and combined it with regenerative signals to develop a multifunctional hydrogel system capable of simultaneously tackling immune dysfunction and regenerative deficiency. Rapid IL-4 release from the methacrylated hyaluronic acid (HAMA) hydrogel exerts a potent immunomodulatory effect by inhibiting the differentiation and function of Th17 cells. Moreover, transforming growth factor-beta1 anchored on methacrylated hyaluronic acid and heparin (HAMA@HepMA) microparticles provides sustained regenerative signals, which synergistically transform the pro-inflammatory microenvironment into a pro-regenerative niche for enhanced OCDs healing. Our study suggests that targeting specific immune pathways can significantly enhance the efficacy of regenerative strategies, paving the way for innovative treatments in orthopedic medicine.

Aims of this study were to compare the functional and radiographic results, perioperative complication after lateral unicompartmental knee arthroplasty (LUKA) with total knee arthroplasty (TKA) and the legacy constrained condylar knee (LCCK) arthroplasty for the treatment of lateral compartmental knee osteoarthritis (LCKOA), and to provide a basis for the treatment of LCKOA. From January 2021 to January 2024, analyzed retrospectively clinical data of 74 patients with LCKOA treated with LUKA, TKA and LCCK arthroplasty. According to the operation plan, the patients were divided into three groups: LUKA group (23 cases), TKA group (23 cases) and LCCK group (28 cases). The changes of hip-knee-ankle (HKA) angle of the affected knee before and after operation were measured. All patients were assessed using the operation time, blood loss during operation, incision length, visual analogue scale (VAS) score before operation and after operation, Hospital for Special Surgery score (HSS), Oxford Knee Score (OKS), range of motion (ROM). All 74 patients were followed up for (2.38 ± 0.33) years. The operation time, blood loss during operation, incision length and VAS score after operation in the LUKA group were significantly less than those in the TKA group and LCCK group (P < 0.05); HKA valgus angle, ROM, HSS score and OKS score of the three groups after operation were significantly better than those before operation (P < 0.05); There was no significant difference among the three groups in HSS score and OKS score (P > 0.05). LUKA, TKA and LCCK arthroplasty have good clinical effect in the treatment of LCKOA; Compared with TKA and LCCK arthroplasty, LUKA has the advantages of less trauma, less bleeding, less pain and quick recovery. The short-term effect is satisfactory, and the long-term effect remains to be observed.