Takahashi Toshiaki, Morris Elisabeth A, Trippel Stephen B
Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
Int J Mol Med. 2007 Jul;20(1):53-7.
Insulin-like growth factor-I (IGF-I) is thought to play an important role in skeletal growth and development through its mitogenic and anabolic effects on epiphyseal growth plate chondrocytes. The bone morphogenetic proteins (BMPs) have been shown to promote endochondral osteogenesis, and some members of the BMP family, including BMP-2 and BMP-9, have anabolic effects on chondrocyte metabolism. We tested the hypothesis that BMP-2 and BMP-9 interact with IGF-I to modulate growth plate chondrocyte mitotic activity. IGF-I, but neither BMP-2 nor BMP-9, stimulated chondrocyte DNA synthesis. However, both BMP-2 and BMP-9 augmented the mitogenic action of IGF-I. BMP-2, but not BMP-9 increased IGF-I binding to growth plate chondrocytes in kinetic studies. In affinity labeling studies, 125I-IGF-I predominantly labeled an Mr approximately 135-kDa moiety, consistent with the alpha subunit of the type 1 IGF receptor and an Mr approximately 250-kDa moiety consistent with the type 2 IGF receptor. 125I-IGF-I labeling also appeared at Mr approximately 43 kDa, consistent with 125I-IGF-I binding to insulin-like growth binding protein-3. Treatment of chondrocytes with BMP-2, but not with BMP-9, increased the intensity of the Mr approximately 135-kDa band and decreased the intensity of the Mr approximately 43-kDa band. Taken together, these data suggest that the BMPs may modulate the action of IGF-I via the type 1 IGF receptor and/or IGF binding proteins.
胰岛素样生长因子-I（IGF-I）被认为通过对骨骺生长板软骨细胞的促有丝分裂和合成代谢作用，在骨骼生长发育中发挥重要作用。骨形态发生蛋白（BMPs）已被证明可促进软骨内成骨，并且BMP家族的一些成员，包括BMP-2和BMP-9，对软骨细胞代谢具有合成代谢作用。我们测试了BMP-2和BMP-9与IGF-I相互作用以调节生长板软骨细胞有丝分裂活性的假说。IGF-I可刺激软骨细胞DNA合成，但BMP-2和BMP-9均无此作用。然而，BMP-2和BMP-9都增强了IGF-I的促有丝分裂作用。动力学研究表明，BMP-2可增加IGF-I与生长板软骨细胞的结合，但BMP-9无此作用。在亲和标记研究中，125I-IGF-I主要标记了一个分子量约为135 kDa的部分，与1型IGF受体的α亚基一致，以及一个分子量约为250 kDa的部分，与2型IGF受体一致。125I-IGF-I标记还出现在分子量约为43 kDa处，与125I-IGF-I与胰岛素样生长结合蛋白-3的结合一致。用BMP-2而非BMP-9处理软骨细胞，增加了分子量约为135 kDa条带的强度，并降低了分子量约为43 kDa条带的强度。综上所述，这些数据表明BMPs可能通过1型IGF受体和/或IGF结合蛋白调节IGF-I的作用。
