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Bone morphogenetic proteins (BMP) are a group of highly conserved functional proteins with a similar structure, belonging to the TGF-β family. BMP stimulates DNA synthesis and cellular replication, thereby promoting the directed differentiation of mesenchymal cells into osteoblasts. It is also a major factor in the induction of bone and cartilage formation in vivo and is expressed during limb growth, endochondral ossification, early fracture, and cartilage repair, and plays an important role in embryonic development and regenerative repair of the skeleton. Deficiency of BMP function usually leads to severe pathologies such as osteogenesis imperfecta (OI), and osteoarthritis. In addition to their obvious osteogenic effects, BMPs are also involved in tumorigenesis and progression and can inhibit cell growth, and proliferation, promote cell differentiation and apoptosis, and so on. Currently, the study of BMPs has involved various disciplines such as embryology, development, genetics, and evolution.
Figure 1. BMP signaling pathways. (Aluganti Narasimhulu C, et al., 2020)
Currently, there are 43 members of the BMP family, which are widely found in tissues such as embryos, blood cells, kidneys, and spleens of pigs, cows, sheep, rabbits, mice, and humans, and there is a high degree of homology among different genera. Among them, BMP-2 is one of the most widely studied BMPs with the strongest osteogenic activity. BMP-2 is one of the most widely studied BMPs with the strongest osteogenic activity, which can induce the directional differentiation and proliferation of undifferentiated mesenchymal stem cells to chondrocytes and osteoblasts, promote osteoblasts' differentiation and maturation, and participate in bone and cartilage growth and development and their reconstruction, thus accelerating the repair of bone defects, and BMP-2 can bind to the receptor on the surface of the cell membrane, activate the intracellular Smad signaling pathway, and promote the metamorphosis of the endometrial stromal cells of the human endometrium.
As a member of the BMPs family, BMP-4 shares a null structure with the general structure of BMPs and plays an important role in promoting bone tissue regeneration and repair. In addition, BMP-4 is also closely related to the induction of embryonic differentiation, guidance of neural stem cell differentiation, regulation of tumor growth and invasion, as well as some cardiovascular and cerebrovascular diseases. Recent studies have shown that BMP-4 may regulate the development of non-alcoholic fatty liver disease (NAFLD) through the regulation of intrahepatic glucose and lipid metabolism, attenuation of insulin resistance, anti-inflammation, and fibrosis. In addition, BMP-4 may also affect NAFLD by regulating the hepatocyte senescence process.
BMP-7 has strong osteoinductive activity and can improve the mechanical properties and function of grafted bone. BMP-7 is one of the most critical BMPs in renal development and is highly expressed in the kidney, which can protect glomerular integrity and have anti-fibrotic effects. It was found that mice deficient in BMP-7 had severe renal defects in addition to eye defects.
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