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Bone morphogenetic protein 2

Definition:

Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and bone formation. Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation. Stimulates also the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation.

References:

[1]. Sascha Keller, et al. Molecular recognition of BMP-2 and BMP receptor IA. Nat Struct Mol Biol. 2004 May;11(5):481-8. [Content Brief]

[2]. J M Wozney, et al. Novel regulators of bone formation: molecular clones and activities. Science. 1988 Dec 16;242(4885):1528-34. [Content Brief]

[3]. F Liu, et al. Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs. Mol Cell Biol. 1995 Jul;15(7):3479-86. [Content Brief]

[4]. Dionys Weber, et al. A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor. BMC Struct Biol. 2007 Feb 12;7:6. [Content Brief]

[5]. Ji Hae Jun, et al. BMP2-activated Erk/MAP kinase stabilizes Runx2 by increasing p300 levels and histone acetyltransferase activity. J Biol Chem. 2010 Nov 19;285(47):36410-9. [Content Brief]

[6]. Howard J Seeherman, et al. A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix. Sci Transl Med. 2019 Apr 24;11(489):eaar4953. [Content Brief]

[7]. Karen Lavery, et al. BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem. 2008 Jul 25;283(30):20948-58. [Content Brief]

[8]. So Tsukahara, et al. Tumour necrosis factor alpha-stimulated gene-6 inhibits osteoblastic differentiation of human mesenchymal stem cells induced by osteogenic differentiation medium and BMP-2. Biochem J. 2006 Sep 15;398(3):595-603. [Content Brief]

[9]. Ken-ichiro Tanaka, et al. Involvement of the osteoinductive factors, Tmem119 and BMP-2, and the ER stress response PERK-eIF2α-ATF4 pathway in the commitment of myoblastic into osteoblastic cells. Calcif Tissue Int. 2014 Apr;94(4):454-64. [Content Brief]

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