Osteoblast-specific expression of MEF induces osteopenia through downregulation of osteoblastogenesis and upregulation of osteoclastogenesis.
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.
Seul
Keyung-Jo
KJ
Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
Cho
Hye-Sim
HS
Heo
Sun-Hee
SH
Baek
Wook-Young
WY
Kim
Jung-Eun
JE
Park
Eui Kyun
EK
Choi
Je-Yong
JY
Ryoo
Hyun-Mo
HM
Cho
Je-Yoel
JY
D016475:3T3 Cells; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000166:cytology; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics*; D055114:X-Ray Microtomography / Q000379:methods
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; D014157:Transcription Factors