当前位置: X-MOL 学术Stem. Cell Rep. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
p38α MAPK Regulates Lineage Commitment and OPG Synthesis of Bone Marrow Stromal Cells to Prevent Bone Loss under Physiological and Pathological Conditions.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2016-03-03 , DOI: 10.1016/j.stemcr.2016.02.001
Qian Cong 1 , Hao Jia 2 , Soma Biswas 1 , Ping Li 1 , Shoutao Qiu 1 , Qi Deng 1 , Xizhi Guo 1 , Gang Ma 1 , Jenny Fang Ling Chau 3 , Yibin Wang 4 , Zhen-Lin Zhang 5 , Xinquan Jiang 6 , Huijuan Liu 1 , Baojie Li 7
Affiliation  

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes. Skewed differentiation of BM-MSCs contributes to the pathogenesis of osteoporosis. Yet how BM-MSC lineage commitment is regulated remains unclear. We show that ablation of p38α in Prx1+ BM-MSCs produced osteoporotic phenotypes, growth plate defects, and increased bone marrow fat, secondary to biased BM-MSC differentiation from osteoblast/chondrocyte to adipocyte and increased osteoclastogenesis and bone resorption. p38α regulates BM-MSC osteogenic commitment through TAK1-NF-κB signaling and osteoclastogenesis through osteoprotegerin (OPG) production by BM-MSCs. Estrogen activates p38α to maintain OPG expression in BM-MSCs to preserve the bone. Ablation of p38α in BM-MSCs positive for Dermo1, a later BM-MSC marker, only affected osteogenic differentiation. Thus, p38α mitogen-activated protein kinase (MAPK) in Prx1+ BM-MSCs acts to preserve the bone by promoting osteogenic lineage commitment and sustaining OPG production. This study thus unravels previously unidentified roles for p38α MAPK in skeletal development and bone remodeling.



中文翻译:

p38αMAPK在生理和病理条件下调节骨髓基质细胞的谱系承诺和OPG合成,以防止骨丢失。

骨髓间充质基质细胞(BM-MSC)能够分化为成骨细胞,软骨细胞和脂肪细胞。BM-MSC的偏向分化有助于骨质疏松症的发病。然而,尚不清楚如何调节BM-MSC沿袭承诺。我们显示,Prx1p38α消融+ BM-MSC产生骨质疏松症表型,生长板缺陷和骨髓脂肪增加,继之以BM-MSC从成骨细胞/软骨细胞向脂肪细胞的偏向分化,并增加破骨细胞生成和骨吸收。p38α通过TAK1-NF-κB信号传导调节BM-MSC的成骨作用,并通过BM-MSC产生的骨保护素(OPG)调节破骨细胞的生成。雌激素激活p38α以维持BM-MSC中OPG的表达,从而保护骨骼。dermo1(后来的BM-MSC标记)阳性的BM-MSC中p38α的消融仅影响成骨分化。因此,Prx1中的p38α丝裂原活化蛋白激酶(MAPK)+ BM-MSC通过促进成骨谱系承诺和维持OPG产生来保护骨骼。因此,本研究揭示了p38αMAPK在骨骼发育和骨骼重塑中的作用。

更新日期:2016-03-03
down
wechat
bug