p38α MAPK Regulates Lineage Commitment and OPG Synthesis of Bone Marrow Stromal Cells to Prevent Bone Loss under Physiological and Pathological Conditions.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cong, Q; Jia, H; Biswas, S; Li, P; Qiu, S; Deng, Q; Guo, X; Ma, G; Ling Chau, JF; Wang, Y; Zhang, Z-L; Jiang, X; Liu, H; Li, B

Published Date

  • April 12, 2016

Published In

Volume / Issue

  • 6 / 4

Start / End Page

  • 566 - 578

PubMed ID

  • 26947973

Pubmed Central ID

  • PMC4834033

Electronic International Standard Serial Number (EISSN)

  • 2213-6711

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2016.02.001

Language

  • eng

Conference Location

  • United States