Nat Med：骨性关节炎机理研究新进展

近日，中国科学院深圳先进技术研究院在骨性关节炎机理与防治方面取得重要研究进展。医药所人体组织与器官退行性研究中心引进深圳市骨与关节退行性疾病防治新技术创新团队与美国约翰霍普金斯医学院、香港大学合作研究，发现骨性关节炎的病理发生机制与软骨下骨及间充质干细胞的迁移有重要相关性。该研究成果5月19日在线发表于《自然·医学》杂志。

骨性关节炎是最常见的一类退行性关节疾病，发病机理尚不清楚，因此目前市场上没有有效的治疗药物。此项研究发现ACLT小鼠模型导致关节受力不均，影响软骨下骨的活性因子TGF-β1的释放，高浓度的TGF-β1诱导了间充质干细胞（MSC）的迁移并形成类骨质岛(osteoid islet)进而加剧了骨性关节炎的形成。然而，在软骨下骨中抑制 TGF-β1活性则显著降低骨性关节炎的发生。这一科学研究加深了对于骨关节炎的认知，并提出了治疗骨性关节炎的新方法。

Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis
Abstract
Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-β1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-β1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-β1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-β activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-β type II receptor (TβRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-β1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.