Bone Morphogenetic Protein 5  (骨形态发生蛋白 5)

骨形态发生蛋白 5 (BMP-5) 是一种多效性的配体蛋白，属于 TGFβ 家族。BMP/TGFβ 信号通路参与血管和瓣膜稳态，这是胚胎发育的关键过程^[1]。BMP/TGFβ 信号可被SMADs (包括 SMAD6 和 SMAD7 ) 终止，SMAD6 和 SMAD7 被 BMP 信号激活和诱导，并通过多种机制关闭 BMP 信号^[2]。BMP-5 沉默后能下调 p38/ERK 信号通路活性抑制软骨细胞衰老和凋亡以及膝关节炎 (OA)^[3]。BMP-5 通过与 I 型受体 BMPR1A 和 II 型受体 BMPR2 结合，启动典型 BMP 信号级联^[4]。BMP-5 还通过 MAPK p38 信号级联等非典型途径触发信号，促进软骨分化^[5]。神经嵴祖细胞中 BMP-5 的特异性表达还可以通过 Mek-Erk-Id3 信号级联诱导细胞增殖，而这种信号级联的中断对细胞存活没有影响^[6]。

Bone Morphogenetic Protein 5 (BMP-5) is a ligand protein with pleiotropic, belongs to TGFβ family. BMP/TGFβ signaling to involve in vascular and valvular homeostasis, which is a critical process of embryonic development^[1]. And BMP/TGFβ signaling can be terminated by inhibitory SMADs including SMAD6 and SMAD7, which are activated and induced by BMP signaling and switch off BMP signaling via multiple mechanisms^[2]. BMP-5 silencing inhibits chondrocyte senescence and apoptosis as well as osteoarthritis (OA) progression by downregulating activity in the p38/ERK signaling pathway^[3]. BMP-5 initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2^[4]. BMP-5 also triggers signal through non-canonical pathway such as MAPK p38 signaling cascade to promote chondrogenic differentiation^[5]. BMP-5 specific expressing in neural crest progenitor cells is sufficient to induce cell proliferation through the Mek-Erk-Id3 signaling cascade, whereas disruption of this signaling cascade had no effect on cell survival^[6].

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