The p75 neurotrophin receptor regulates MC3T3-E1 osteoblastic differentiation

被引:26
作者
Mikami, Yoshikazu [1 ,2 ]
Suzuki, Shinnosuke [1 ]
Ishii, Yumiko [3 ]
Watanabe, Nobukazu [4 ]
Takahashi, Tomihisa [1 ,2 ]
Isokawa, Keitaro [1 ,2 ]
Honda, Masaki J. [1 ,2 ]
机构
[1] Nihon Univ, Sch Dent, Dept Anat, Tokyo 1018310, Japan
[2] Nihon Univ, Sch Dent, Dent Res Ctr, Tokyo 1018310, Japan
[3] Univ Tokyo, Inst Med Sci, FACS Core Lab, Tokyo 1088639, Japan
[4] Univ Tokyo, Inst Med Sci, Lab Diagnost Med, Tokyo 1088639, Japan
关键词
MC3T3-E1; Cells; Osteoblast; Osteogenic differentiation; p75(NTR); Trk; MESENCHYMAL STEM-CELLS; NERVE GROWTH-FACTOR; TRANSCRIPTION FACTOR; STROMAL CELLS; IN-VITRO; APOPTOSIS; EXPRESSION; DISRUPTION; INDUCTION; OSTERIX;
D O I
10.1016/j.diff.2012.07.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
While the role of p75(NTR) signaling in the regulation of nerve-related cell growth and survival has been well documented, its actions in osteoblasts are poorly understood. In this study, we examined the effects of p75(NTR) on osteoblast proliferation and differentiation using the MC3T3-E1 pre-osteoblast cell line. Proliferation and osteogenic differentiation were significantly enhanced in p75(NTR)-overexpressing MC3T3-E1 cells (p75GFP-E1). In addition, expression of osteoblast-specific osteocalcin (OCN), bone sialoprotein (BSP), and osterix mRNA, ALP activity, and mineralization capacity were dramatically enhanced in p75GFP-E1 cells, compared to wild MC3T3-E1 cells (GFP-E1). To determine the binding partner of p75(NTR) in p75GFP-E1 cells during osteogenic differentiation, we examined the expression of trkA, trkB, and trkC that are known binding partners of p75(NTR), as well as NgR. Pharmacological inhibition of trk tyrosine kinase with the K252a inhibitor resulted in marked reduction in the level of ALPase under osteogenic conditions. The deletion of the GDI binding domain in the p75(NTR)-GFP construct had no effect on mineralization. Taken together, our studies demonstrated that p75(NTR) signaling through the trk tyrosine kinase pathway affects osteoblast functions by targeting osteoblast proliferation and differentiation.
引用
收藏
页码:392 / 399
页数:8
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