Bone Morphogenetic Proteins (BMPs)

Bone Morphogenetic Protein 2 (BMP-2) is a ligand protein with pleiotropic, belongs to TNFβ family. BMP-2 formats BMP/TGFβ signaling to involve in vascular and valvular homeostasis, which is a critical process of embryonic development^[1]. BMP-2/TGFβ 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^[2]. BMP-2 is widely found in different animals, while the sequence in human is similar to Rat (91.86%), and mouse (92.13%). BMPs exhibits critical contributions to the pathophysiology of atherosclerosis, pulmonary vascular disease, and vascular and valvular calcification^[1]. BMP-2 binds different receptor, such as type I receptors (ALK-2/-3/-6) and type II receptors (BMPR2, ACVR2A), to regulate various calcification type^[1]. BMP-2 promotes monocyte infiltration and inflammation of atherosclerotic legions^[3]. It is linked to increased plaque formation via pro-inflammatory and pro-atherogenic effects, promoting oxidative stress, endothelial dysfunction and osteogenic differentiation^[4]. BMP-2 is overexpressed in ossified regions of human calcified valves by myofibroblasts and pre-osteoblasts in areas densely infiltrated with B- and T-lymphocytes^[5]. And it serves as the linkers between atherosclerotic vascular calcification with mechanisms of normal bone formation^[6]. BMP-2 induces angiogenesis, endothelial cells (ECs) proliferation, and migration^[7]. And BMP-2 also enhances the expression of the osteoblast and chondrocyte master transcriptional regulator RUNX2 to promote the mineralization of cultured human coronary vascular SMCs in a manner that was dependent on oxidative stress and endoplasmic reticulum (ER) stress^[8].