Bone Morphogenetic Protein 1

Bone morphogenetic protein 1 (BMP-1) also known as metalloprotease, belonging to the BMP-1/tolloidlike proteinases (BTP) family^[1][2]. BTPs are known to be involved in the control of muscle growth and homeostasis and in wound healing and tissue repair, and BMP-1 is a signature extracellular matrix (ECM) proteins associated with the high metastatic potential of breast tumors^[3]. BMP-1 regulates morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8^[4]. BMP-1 is the dominant C-proteinase in postnatal lung fibroblasts and mediates cleavage of COOH-terminal propeptide of type I procollagen (CICP) with the main action site of extracellular space^[1]. BMP-1 maintains appropriate levels of procollagen I and its activated products, acts as an essential part for maintaining periodontal homeostasis and normal cementum formation^[2]. The cleavage of thrombospondin-1 (TSP-1), an ECM protein classified as “matricellular” for its ability to regulate cell-matrix interactions, results BMP-1 overexpression. However BMP-1 can both trigger the disruption of cell adhesion and stimulate TGF-β signaling in TSP-1-rich microenvironments, which promote the differentiation of primary human keratocytes into myofibroblasts^[3]. Thereby, BMP-1 participates in several developmental and physiological processes such as cartilage and bone formation, muscle growth and homeostasis^[2][3]. Mutations of BMP-1 gene cause osteogenesis imperfecta in human, a bone disorder characterized by brittle bones that are prone to fracture, or phenotypes of periodontal disease and skin fragility in mice^[3]. BMP-1-3 is a novel systemic regulator of bone repair. BMP-1-3 isoform of the BMP-1 gene circulates in the human plasma and enhances bone healing. In vitro BMP-1-3 increases the expression of collagen type I and osteocalcin in MC3T3-E(1) osteoblast like cells, and enhances the formation of mineralized bone nodules from bone marrow mesenchymal stem cells^[4].

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