Nmp4 Promotes TNFα-induced Apoptosis in Primary Osteoblasts
YANG Zhou-Qi 1） , Fredrick M. Pavalko 2），SHANG Peng 1）
(1)Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, Faculty of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China; 2)Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA)
Abstract：Abstract Skeletal diseases including osteoporosis are due to, in part, dysregulation on apoptosis of osteoblasts. Previous studies revealed that nuclear matrix protein 4 (Nmp4) acted via negative regulation on the differentiation and proliferation of osteoblasts and suppressed the increases in the bone mineral density and bone mass in vivo. In this study, we investigated whether Nmp4 is involved in regulating TNFα-induced apoptosis of primary calvarial osteoblasts isolated from Nmp4 knockout (Nmp4-KO) and widetype (WT) mice. The results showed that Nmp4-deficiency suppressed TNFα-induced activation of caspase-3 in primary osteoblasts. Futhermore, associated apoptotic signaling molecules including phosphorylated Erk, Akt and JNK, were detected. After treating with TNF-α (10ng/ml) and cycloheximide (CHX, 10μg/ml) for 6 hours, Erk, Akt and JNK were significantly activated in Nmp4-KO and WT osteoblasts. The levels of phosphorylated Erk and Akt in the treated Nmp4-KO osteoblasts were notably higher than that in the treated WT controls, meanwhile the TNFα-induced activation of JNK was significantly inhibited in Nmp4-KO osteoblasts as compared to treated WT controls. Two hours treatment with TNFα/CHX promoted NFκB(p65) phosphorylation and its nuclear translocation. Interestingly, the level of phosphorylated NFκB(p65) in untreated Nmp4-KO osteoblasts is distinctly higher than that in untreated WT controls. However, Nmp4 has not effects on the phosphorylation of pro-apoptoric Bad and the expression of anti-apoptotic Bcl-xl. In conclusion, Nmp4-deficiency inhibits TNFα-induced apotosis in primary mouse osteoblasts via activating anti-apoptotic signaling molecules and restraining pro-apoptotic signaling pathway.
杨周岐 , Fredrick M. Pavalko，商澎. Nmp4促进TNF-α诱导的成骨细胞凋亡[J]. 中国生物化学与分子生物学报, 2010, 26(9): 828-835.
YANG Zhou-Qi , Fredrick M. Pavalko，SHANG Peng. Nmp4 Promotes TNFα-induced Apoptosis in Primary Osteoblasts. Chinese Journal of Biochemistry and Molecular Biol, 2010, 26(9): 828-835.
