(Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, Faculty of Life Sciences, Northwestern Polytechnical University, Xian 710072 , China)
Abstract:Nuclear matrix protein 4 (Nmp4), also identified as cas-interacting zinc finger protein (CIZ), is a transcription factor localized at the focal adhension sites and also in the nucleus. Nmp4/CIZ reduces bone mineral density (BMD) and bone mass by inhibiting bone formation in vivo, but not affecting bone resorption parameters. Through binding to the upstream regulatory regions of type I collagen and matrix metalloproteinase promoters, Nmp4/CIZ inhibits synthesis of type I collagen and upregulates expression of matrix metalloproteinases, thereby accelerates the bone turnover. Nmp4/CIZ suppresses proliferation and promotes apoptosis of osteoblasts, also downregulates the differentiation of osteoblasts induced by bone morphogenic protein and parathyroid hormone. The bone mass loss induced by tail suspension was significantly attenuated in Nmp4 knockout (Nmp4-KO) mice compared to those of the widetype (WT) controls. In addition, the Nmp4-deficiency promoted the flow shear stress-induced β-catenin signaling pathway in osteoblasts. These suggested that Nmp4/CIZ was an important molecule to regulate th e mechanotransduction in bone cells and susceptible to the changes in the mechanical environment. Both in vivo and in vitro experimental results demonstrated that Nmp4/CIZ acted as a negative regulator and could be a potential novel drug target to resist osteoporosis or bone loss.
杨周岐,商澎. Nmp4/CIZ对成骨细胞功能的调节作用[J]. 中国生物化学与分子生物学报, 2010, 26(06): 498-504.
YANGZhou-Qi,SHANGPeng. Regulatory Role of Nmp4/CIZ in Osteoblasts. Chinese Journal of Biochemistry and Molecular Biol, 2010, 26(06): 498-504.