Cornell University, Ithaca, NY, USA.
Hospital for Special Surgery, New York, NY, USA.
Sci Adv. 2024 Apr 19;10(16):eadk8402. doi: 10.1126/sciadv.adk8402.
Osteoarthritis (OA) treatment is limited by the lack of effective nonsurgical interventions to slow disease progression. Here, we examined the contributions of the subchondral bone properties to OA development. We used parathyroid hormone (PTH) to modulate bone mass before OA initiation and alendronate (ALN) to inhibit bone remodeling during OA progression. We examined the spatiotemporal progression of joint damage by combining histopathological and transcriptomic analyses across joint tissues. The additive effect of PTH pretreatment before OA initiation and ALN treatment during OA progression most effectively attenuated load-induced OA pathology. Individually, PTH directly improved cartilage health and slowed the development of cartilage damage, whereas ALN primarily attenuated subchondral bone changes associated with OA progression. Joint damage reflected early transcriptomic changes. With both treatments, the structural changes were associated with early modulation of immunoregulation and immunoresponse pathways that may contribute to disease mechanisms. Overall, our results demonstrate the potential of subchondral bone-modifying therapies to slow the progression of OA.
骨关节炎 (OA) 的治疗受到缺乏有效非手术干预措施以减缓疾病进展的限制。在这里，我们研究了软骨下骨特性对 OA 发展的贡献。我们在 OA 发病前使用甲状旁腺激素 (PTH) 来调节骨量，在 OA 进展期间使用阿仑膦酸钠 (ALN) 来抑制骨重塑。我们通过结合关节组织的组织病理学和转录组学分析来检查关节损伤的时空进展。在 OA 发病前进行 PTH 预处理和在 OA 进展期间进行 ALN 治疗的联合作用最有效地减轻了负荷诱导的 OA 病理。单独使用时，PTH 可直接改善软骨健康并减缓软骨损伤的发展，而 ALN 主要减轻与 OA 进展相关的软骨下骨变化。关节损伤反映了早期转录组变化。在这两种治疗方法中，结构变化与免疫调节和免疫反应途径的早期调节相关，这些途径可能有助于疾病机制。总体而言，我们的研究结果表明，软骨下骨修饰疗法具有减缓 OA 进展的潜力。
