间充质干细胞对破骨细胞形成的影响

Modulatory effects of mesenchymal stem cells on osteoclast formation

近年来研究发现间充质干细胞（MSCs）具有组织修复及免疫抑制作用,因此用于多种自身免疫性及退行性疾病的治疗。MSCs的成骨分化功能在骨重建过程中发挥着重要作用。已有研究将MSCs注入胶原诱导的关节炎大鼠及类风湿关节炎（RA）患者的炎性关节中以进行治疗,然而,MSCs如何在关节中发挥作用尚未阐明,且关于MSCs对破骨细胞形成及骨再吸收作用的影响的研究鲜有报道。在生理条件下,MSCs可通过生成核因子κB（NF-κB）受体激活蛋白配体（RANKL）及巨噬细胞集落刺激因子（M-CSF）等促破骨细胞形成因子促进破骨细胞形成;但在炎性条件下,MSCs则可通过生成护骨因子（OPG）抑制破骨细胞的形成。因此MSCs具有双重作用,其对破骨细胞形成的作用取决于所处的炎性环境,这些作用有望用于骨破坏相关炎性疾病的治疗。

Mesenchymal stem cells（ MSCs） by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. Osteogenic differentiation of MSCs is important for homeostatic bone remodeling. Infiltration of MSCs into inflamed joints has been reported in collagen-induced arthritis murine model and in patients with rheumatoid arthritis（ RA）. However,the underlying mechanisms on how MSC acts in the joints remain elusive. And few studies addressed the effect of MSCs on osteoclastogenesis and bone resorption. Under physiological conditions,MSCs support osteoclastogenesis through producing the main osteoclastogenic cytokines,RANKL and M-CSF. However,during inflammation,MSCs suppress osteoclast formation and activity,partly via secretion of the key antiosteoclastogenic factor,osteoprotegerin（ OPG）. MSCs thus seem to exert a dual effect,by stimulating or inhibiting osteoclastogenesis,depending on the inflammatory milieu. This effect of MSCs on osteoclast formation may be exploited for the therapeutic potential of MSCs in bone loss associated with inflammatory diseases.