BMP-3B/GDF10  (生长分化因子 10)

骨形态发生蛋白 3 (BMP-3) 是一种多效性配体蛋白，属于 TGFβ 家族。BMP-3 是成骨素的主要成分，具有成骨活性^[1]。BMP-3 广泛存在于不同的动物中，而人的序列与大鼠和小鼠的序列相似性分别为 81.94% 和小鼠 80.86%。由于 BMP-3 在癌细胞系中高甲基化，蛋白表达显著降低，因此 BMP-3 可作为筛选结直肠癌 (CRC) 的可靠生物标志物^[2]。BMP-3 还在致癌过程中发挥抑制作用，通过 ActRIIB/SMAD2 依赖性和 TAK1/JNK 信号通路抑制结肠肿瘤的发生^[2]。BMP-3 可对不同细胞类型的激活素信号发挥双向调节作用。BMP-3 可刺激人间充质干细胞增殖，这一作用也会受到 TGF-β/激活素受体激酶抑制剂的抑制^[3]。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^[4]。BMP/TGFβ 信号被抑制 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^[5]。

Bone Morphogenetic Protein 3 (BMP-3) is a ligand protein with pleiotropic, belongs to TGFβ family. BMP-3 is a major component of osteogenin, which has osteogenic activity^[1]. BMP-3 is widely found in different animals, while the sequence in human is lowly similar to Rat (81.94%), and mouse (80.86%). BMP-3 particularly serves as a reliable biomarker for screening colorectal cancer (CRC) because BMP-3 is hypermethylated and its protein expression is significantly reduced in cancer cell lines^[2]. BMP-3 also plays a suppressor role in carcinogenesis, suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and TAK1/JNK signaling pathways^[2]. BMP-3 could exert two-way regulatory effects on activin signaling in distinct cell types. BMP-3 stimulates proliferation of human mesenchymal stem cells which could be blocked by TGF-β/activin receptor kinase inhibitors^[3]. BMP/TGFβ signaling to involve in vascular and valvular homeostasis, which is a critical process of embryonic development^[4]. And the 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^[5].

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