Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

被引:37
|
作者
Salazar, Valerie S. [1 ]
Ohte, Satoshi [1 ,2 ]
Capelo, Luciane P. [1 ,3 ]
Gamer, Laura [1 ]
Rosen, Vicki [1 ]
机构
[1] Harvard Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA
[2] Saitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, 1397-1 Yamane, Hidaka, Saitama 3501241, Japan
[3] Univ Fed Sao Paulo, Inst Ciencia & Tecnol, Rua Talim 330, BR-12231280 Sao Jose Dos Campos, SP, Brazil
来源
DEVELOPMENT | 2016年 / 143卷 / 23期
关键词
BMP; Wnt; Osteoblast; Osx1; Sp7; Dlx5; Grhl3; Mouse MLB13 cells; CARBONIC-ANHYDRASE; BONE-FORMATION; OSTERIX EXPRESSION; STROMAL CELLS; SAOS-2; CELLS; STEM-CELL; DIFFERENTIATION; IDENTIFICATION; TRANSCRIPTION; MUTATION;
D O I
10.1242/dev.136879
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Enhanced BMP or canonical Wnt (cWnt) signaling are therapeutic strategies employed to enhance bone formation and fracture repair, but the mechanisms each pathway utilizes to specify cell fate of bone-forming osteoblasts remain poorly understood. Among all BMPs expressed in bone, we find that singular deficiency of Bmp2 blocks the ability of cWnt signaling to specify osteoblasts from limb bud or bone marrow progenitors. When exposed to cWnts, Bmp2-deficient cells fail to progress through the Runx2/Osx1 checkpoint and thus do not upregulate multiple genes controlling mineral metabolism in osteoblasts. Cells lacking Bmp2 after induction of Osx1 differentiate normally in response to cWnts, suggesting that pre-Osx1(+) osteoprogenitors are an essential source and a target of BMP2. Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) as a transcription factor in the osteoblast gene regulatory network induced during bone development and bone repair, which acts upstream of Osx1 in a BMP2-dependent manner. The Runx2/Osx1 transition therefore receives crucial regulatory inputs from BMP2 that are not compensated for by cWnt signaling, and this is mediated at least in part by induction and activation of Grhl3.
引用
收藏
页码:4352 / 4367
页数:16
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