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].
- [1]. N'Diaye EN, et al. Extracellular BMP-1 is the major proteinase for COOH-terminal proteolysis of type I procollagen in lung fibroblasts. Am J Physiol Cell Physiol. 2021 Feb 1;320(2):C162-C174. [Content Brief]
- [2]. Wang J, et al. Proteinase bone morphogenetic protein 1, but not tolloid-like 1, plays a dominant role in maintaining periodontal homeostasis. J Periodontol. 2021 Jul;92(7):1018-1029. [Content Brief]
- [3]. Anastasi C, et al. BMP-1 disrupts cell adhesion and enhances TGF-β activation through cleavage of the matricellular protein thrombospondin-1. Sci Signal. 2020 Jul 7;13(639):eaba3880. [Content Brief]
- [4]. Grgurevic L, et al. Bone morphogenetic protein (BMP)1-3 enhances bone repair. Biochem Biophys Res Commun. 2011 Apr 29;408(1):25-31. [Content Brief]
