骨质疏松症 z-bo 2020-09-18 514

　　Researchers from Xi’an Jiaotong University and the Fourth Military Medical University have confirmed in a new study that Discoid Domain Receptor 2 (DDR2) inhibits osteoclast production, thus pointing out a potential therapeutic target for osteoporosis point.

　　Leading this research is Professor Xu Li from the First Affiliated Hospital of Xi’an Jiaotong University School of Medicine. He has been engaged in medical genetics and tumor cell molecular genetics research, and has published more than 100 papers in academic journals at home and abroad.

　　Osteoporosis is due to the imbalance of bone metabolism. The destruction of bone is greater than the production of bone, which leads to a decrease in bone mass per unit volume in bone cells (mainly reduction of calcium, phosphorus, and protein matrix), bone tissue microstructure degeneration, and bone The fragility of the bones increases, so that the systemic bone disease prone to fractures. If it is not treated early, it will bring serious consequences such as pain, shortening of height, hunchback, decreased respiratory function, and even fractures. As a systemic metabolic disease, osteoporosis is currently the world's disease with a large morbidity, fatality rate and health care costs. With the aging population, osteoporosis not only threatens the health of the elderly, especially women, Xi’an Jiaotong University, the Fourth Military Medical University and other researchers have confirmed in a new study that discoid domain receptor 2 (DDR2) inhibits The production of osteoporotic cells and possibly the treatment of osteoporosis. Point out the goal. point. Professor Xu Li (XuLi) of the First Affiliated Hospital of Xi'an Jiaotong University School of Medicine led the research. He is engaged in the research of medical genetics and tumor cell molecular genetics, and has published more than 100 papers in academic journals at home and abroad.

　　Osteoporosis is caused by the imbalance of bone metabolism, bone destruction is greater than bone production, bone mass per unit volume of bone cells is reduced (mainly calcium, phosphorus, protein matrix loss), and leads to the degradation of the microstructure of bone tissue. Systemic bone disease increases the fragility of the bones, so fractures are more likely to occur. If not treated early, it can cause serious consequences, such as pain, shortened height, swelling, decreased respiratory function and even fractures. Osteoporosis is a systemic metabolic disease. It is currently a global disease with high morbidity, mortality and medical costs. With the aging of the population, osteoporosis not only threatens the health of the elderly, especially women, but also becomes a serious social problem. DDR2 is a member of receptor tyrosine kinases and is mainly expressed in lung, skeletal muscle, heart muscle, kidney and skin. Its main ligands are type I, type III and type X collagen fibers. When DDR2 binds to collagen ligands, it activates its own tyrosine residues, which leads to the activation of downstream signaling molecules, leading to the development of multicellular organisms, tumors, arthritis, and atherosclerosis of cells and ECM. Mediated signals play an important role in the process of sclerosis and pulmonary fibrosis. Recent studies have shown that DDR2 promotes osteoblast differentiation and bone formation.

　　In this new study, we investigated the role of DDR2 in the formation of osteoclasts and bone-absorbing cells. They found that the differentiated bone disease cells had catalytically active DDR2, but its abundance was reduced. The overexpression of DD2 can inhibit the formation of osteoblast markers in the bone matrix culture model, osteoblast maturation and osteoblast-mediated bone resorption. On the contrary, the inhibitory effect of RNA interference on Ddr2 can accelerate the differentiation of osteoclasts and the absorption of mouse bones. In addition, researchers have confirmed that the co-receptor Neuropyrin-1 (Nrp1) is a DDR2 interacting protein. By forming the DDR2-Nrp1-PlexinA1 complex, DDR2 promotes the binding of Nrp1 to the co-receptor PlexinA1, and blocks the stimulation of the clavicle production mediated by PlexinA1. DDR2 prevents Plexin A1 from interacting with the receptor TREM2 and the adaptor protein DAP12. They found that inhibiting Nrp1 in cells overexpressing DDR2 can restore the expression of bone disease markers, while ectopic expression of Nrp1 can inhibit the induction of bone disease in DDR2 silent cells. .. In mice, Nrp1 enhances the function of DDR2 to promote osteoblast differentiation and bone formation. In a mouse model of osteoporosis ovalectomy, the researchers used adenovirus to deliver DDR2 to the femur, thereby reducing the phenotype of osteoporosis. These results indicate that DDR2 is an inhibitor of osteoblast formation and a promoter of osteoblast production, and the increase of DDR2 is a potential treatment strategy for patients with osteoporosis. It shows the possibilities.

　　康, and become a serious social problem.

　　DDR2 is a member of receptor tyrosine kinases and is mainly expressed in lung, skeletal muscle, myocardium, kidney and skin. Its main ligand is type I, type III and type X collagen fibers. When DDR2 binds to the collagen ligand, it activates its own tyrosine residues, leading to the activation of downstream signal molecules, mediating the signal transduction of cells and ECM, in the development of multicellular organisms, tumors, arthritis, atherosclerosis Play an important role in the process of hardening and pulmonary fibrosis. Recent studies have found that DDR2 promotes osteoblast differentiation and bone formation.

　　In this new study, the researchers explored the role of DDR2 in the formation of osteoclasts, cells that perform bone resorption. They found that although differentiated osteoclasts have catalytically active DDR2, their abundance decreased. Overexpression of DD2 can inhibit the formation of osteoclast markers, osteoclast maturation, and osteoclast-mediated bone resorption in the bone matrix culture model. In contrast, inhibition of Ddr2 by RNA interference can accelerate osteoclast differentiation and bone resorption in mice.

　　In addition, the researchers also determined that the co-receptor Neuropilin-1 (Nrp1) is an interacting protein of DDR2. By forming the DDR2-Nrp1-PlexinA1 complex, DDR2 promotes the binding of Nrp1 to the co-receptor PlexinA1 and blocks the PlexinA1-mediated stimulation of osteoclast production. DDR2 prevents PlexinA1 from interacting with the receptor TREM2 and the adaptor protein DAP12.

　　They confirmed that inhibiting Nrp1 in cells overexpressing DDR2 can restore the expression of osteoclast markers, while ectopic expression of Nrp1 in DDR2 silent cells can inhibit the induction of osteoclastogenesis. In mice, Nrp1 enhanced the function of DDR2 to promote osteoblast differentiation and bone formation. In an ovariectomized mouse model of osteoporosis, the researchers used adenovirus to deliver DDR2 to the femur to reduce the osteoporotic phenotype.

　　These results reveal that DDR2 is an inhibitor of osteoclastogenesis and a promoter of osteoblastogenesis, indicating that increasing DDR2 may be a potential treatment strategy for patients with osteoporosis.