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Osteoblast‐specific expression of MEF induces osteopenia through downregulation of osteoblastogenesis and upregulation of osteoclastogenesis
Author(s) -
Seul KeyungJo,
Cho HyeSim,
Heo SunHee,
Baek WookYoung,
Kim JungEun,
Park Eui Kyun,
Choi JeYong,
Ryoo HyunMo,
Cho JeYoel
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.208
Subject(s) - osteoblast , downregulation and upregulation , genetically modified mouse , runx2 , bone resorption , transgene , osteopenia , bone remodeling , chemistry , microbiology and biotechnology , endocrinology , medicine , osteoporosis , cancer research , bone mineral , biology , in vitro , gene , biochemistry
In bone remodeling, various transcriptional factors are involved, and the deficiency or overexpression of some of these factors results in bone defects. Myeloid elf‐1‐like factor (MEF) is one of the Ets transcription factors that control the expression of genes that are critical for biologic processes such as cell proliferation, differentiation, and death. Previously, we reported that MEF promotes cell proliferation and functions as a negative regulator of osteogenic differentiation by interacting directly with Runx2 and suppressing its transcriptional activity. To investigate the in vivo function of MEF in bone formation and bone remodeling in vivo, we generated transgenic mice that overexpress MEF in osteoblasts under the control of the 2.3‐kb Col1α1 promoter, named Col1α1‐MEF. Femoral bone in Col1α1‐MEF transgenic mice exhibited low bone mass with fewer trabecular bones and thinner and less developed cortical bones. The mineralized volume fraction (BV/TV) and bone‐forming rate (BFR) were remarkably decreased to about 63% and 40%, respectively, in 6‐week‐old MEF transgenic mice compared with wild‐type mice. In addition, reduced bone mineral density was observed in lumbar vertebrae of Col1α1‐MEF transgenic mice. The number of TRACP + osteoclasts was increased in Col1α1‐MEF transgenic mice and MEF‐overexpressing MC3T3‐E1 cells. All these in vivo results suggest that MEF suppresses bone formation by osteoblasts and facilitates bone resorption by activating osteoclasts indirectly. © 2011 American Society for Bone and Mineral Research.