Growth Differentiation Factor 5 (GDF-5)  (生长分化因子-5)

GDF-5 属于 TGFβ 超家族。GDF-5 对于软骨发育和稳态至关重要，GDF-5 缺乏与骨关节炎 (OA) 相关。具体而言，GDF-5 对 BMPR-IB、BMPR-II 和激活素 II 型受体具有高结合亲和力。与其受体结合后，GDF-5 的信号级联激活下游 Smad 通路。然后，磷酸化的 Smad 1/5/8与 Smad 4 形成复合物并易位到细胞核中，从而调节细胞过程，例如 ECM 的增殖、分化和合成^[1]。GDF-5 可以调节软骨形成的初始阶段 (通过增加细胞粘附的间质凝集)，或促进骨骼发育过程中的软骨细胞增殖^[2]。人 GDF-5 与小鼠的氨基酸序列同源性约 91%。

GDF-5 belongs to TGFβ superfamily. GDF-5 is essential for cartilage development and homeostasis, and GDF-5 deficiency is associated with osteoarthritis (OA). Specifically, GDF-5 has high binding affinity to BMPR-IB, BMPR-II and Activin type II receptors. Upon binding to the receptors, the signalling cascade of GDF-5 activates the downstream Smad pathway. The phosphorylated Smad 1/5/8 then forms the complex with Smad 4 and translocates into the nucleus, thereby regulating cellular processes, such as proliferation, differentiation and synthesis of the ECM^[1]. GDF-5 can modulate the initial stages of chondrogenesis (the mesenchymal condensations by increasing cell adhesion), or increase chondrocyte proliferation during skeletal development^[2]. Human GDF-5 shares about 91% aa sequence identity with mouse.

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