Bone Size and Quality Regulation: Concerted Actions of mTOR in Mesenchymal Stromal Cells and Osteoclasts

Hongguang Wu, Zhixiang Wu, Ping Li, Qian Cong, Rongrong Chen, Wenrui Xu, Soma Biswas, Huijuan Liu, Xuechun Xia, Shanshan Li, Weiwei Hu, Zhenlin Zhang, Samy L. Habib, Lingli Zhang, Jun Zou, Hongbing Zhang, Weihong Zhang, Baojie Li

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The bone size and quality, acquired during adolescent growth under the influence of anabolic hormones, growth factors, and nutrients, determine the height and bone stability and forecast osteoporosis risks in late life. Yet bone size and quality control mechanisms remain enigmatic. To study the roles of mammalian target of rapamycin (mTOR) signaling, sensor of growth factors and nutrients, in bone size and quality regulation, we ablated Tsc1, a suppressor of mTOR, in mesenchymal stromal cells (MSCs), monocytes, or their progenies osteoblasts and osteoclasts. mTOR activation in MSCs, but much less in osteoblasts, increased bone width and mass due to MSC hyperproliferation, but decreased bone length and mineral contents due to defective MSC differentiation. mTOR activation promotes bone mineral accretion by inhibiting osteoclast differentiation and activity directly or via coupling with MSCs. Tuberous sclerosis complex patient studies confirmed these findings. Thus, mTOR regulates bone size via MSCs and bone quality by suppressing catabolic activities of osteoclasts.

Original languageEnglish (US)
Pages (from-to)1600-1616
Number of pages17
JournalStem Cell Reports
Volume8
Issue number6
DOIs
StatePublished - Jun 6 2017

Keywords

  • MSCs
  • TSC patient
  • bone
  • cartilage
  • mTOR
  • mesenchymal stromal cells
  • monocyte
  • osteoclast
  • rapamycin

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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