Targeting TGFβ signaling in subchondral bone and articular cartilage homeostasis.

Targeting TGFβ signaling in subchondral bone and articular cartilage homeostasis.
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DOI:
10.1016/j.tips.2014.03.005
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发表时间:
2014-05
影响因子:
13.8
通讯作者:
Cao, Xu
Cao, Xu
中科院分区:
医学1区
文献类型:
--
作者:
Zhen, Gehua;Cao, Xu

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骨关节炎(OA)是最常见的退行性关节疾病,目前还没有针对OA的疾病改善疗法。单独靶向关节软骨可能不足以阻止这种疾病的进展。关节软骨和软骨下骨作为一个功能单位。越来越多的证据表明,转化生长因子β(transforming growth factor β,TGFβ)在维持关节软骨和软骨下骨的稳态中起着重要作用。在适当的时间和部位激活细胞外基质潜伏性TGFβ是其发挥功能的前提。在骨关节炎发病时,软骨下骨对异常机械负荷环境的异常活化诱导了类固醇胰岛的形成。结果,软骨下骨结构的改变改变了关节软骨上的应力分布,导致其退变。因此,抑制软骨下骨中的TGFβ活性可能为OA的治疗提供新的途径。本文就TGFβ在关节软骨和软骨下骨稳态中的作用作为OA治疗的新靶点进行综述。
Osteoarthritis (OA) is the most common degenerative joint disease, and there is no disease-modifying therapy for OA currently available. Targeting of articular cartilage alone may not be sufficient to halt this disease progression. Articular cartilage and subchondral bone act as a functional unit. Increasing evidence indicates that transforming growth factor β (TGFβ) plays a crucial role in maintaining homeostasis of both articular cartilage and subchondral bone. Activation of extracellular matrix latent TGFβ at the appropriate time and location is the prerequisite for its function. Aberrant activation of TGFβ in the subchondral bone in response to abnormal mechanical loading environment induces formation of osteroid islets at onset of osteoarthritis. As a result, alteration of subchondral bone structure changes the stress distribution on the articular cartilage and leads to its degeneration. Thus, inhibition of TGFβ activity in the subchondral bone may provide a new avenue of treatment for OA. In this review, we will respectively discuss the role of TGFβ in homeostasis of articular cartilage and subchondral bone as a novel target for OA therapy.
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