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p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner.

Publication ,  Journal Article
Cong, Q; Jia, H; Li, P; Qiu, S; Yeh, J; Wang, Y; Zhang, Z-L; Ao, J; Li, B; Liu, H
Published in: Sci Rep
April 6, 2017

Bone mass is determined by the balance between bone formation, carried out by mesenchymal stem cell-derived osteoblasts, and bone resorption, carried out by monocyte-derived osteoclasts. Here we investigated the potential roles of p38 MAPKs, which are activated by growth factors and cytokines including RANKL and BMPs, in osteoclastogenesis and bone resorption by ablating p38α MAPK in LysM+monocytes. p38α deficiency promoted monocyte proliferation but regulated monocyte osteoclastic differentiation in a cell-density dependent manner, with proliferating p38α-/- cultures showing increased differentiation. While young mutant mice showed minor increase in bone mass, 6-month-old mutant mice developed osteoporosis, associated with an increase in osteoclastogenesis and bone resorption and an increase in the pool of monocytes. Moreover, monocyte-specific p38α ablation resulted in a decrease in bone formation and the number of bone marrow mesenchymal stem/stromal cells, likely due to decreased expression of PDGF-AA and BMP2. The expression of PDGF-AA and BMP2 was positively regulated by the p38 MAPK-Creb axis in osteoclasts, with the promoters of PDGF-AA and BMP2 having Creb binding sites. These findings uncovered the molecular mechanisms by which p38α MAPK regulates osteoclastogenesis and coordinates osteoclastogenesis and osteoblastogenesis.

Duke Scholars

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

April 6, 2017

Volume

7

Start / End Page

45964

Location

England

Related Subject Headings

  • X-Ray Microtomography
  • Stem Cells
  • Platelet-Derived Growth Factor
  • Phenotype
  • Osteoporosis
  • Osteogenesis
  • Osteoclasts
  • Monocytes
  • Mitogen-Activated Protein Kinase 14
  • Mice
 

Citation

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Cong, Q., Jia, H., Li, P., Qiu, S., Yeh, J., Wang, Y., … Liu, H. (2017). p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner. Sci Rep, 7, 45964. https://doi.org/10.1038/srep45964
Cong, Qian, Hao Jia, Ping Li, Shoutao Qiu, James Yeh, Yibin Wang, Zhen-Lin Zhang, Junping Ao, Baojie Li, and Huijuan Liu. “p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner.Sci Rep 7 (April 6, 2017): 45964. https://doi.org/10.1038/srep45964.
Cong, Qian, et al. “p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner.Sci Rep, vol. 7, Apr. 2017, p. 45964. Pubmed, doi:10.1038/srep45964.
Cong Q, Jia H, Li P, Qiu S, Yeh J, Wang Y, Zhang Z-L, Ao J, Li B, Liu H. p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner. Sci Rep. 2017 Apr 6;7:45964.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

April 6, 2017

Volume

7

Start / End Page

45964

Location

England

Related Subject Headings

  • X-Ray Microtomography
  • Stem Cells
  • Platelet-Derived Growth Factor
  • Phenotype
  • Osteoporosis
  • Osteogenesis
  • Osteoclasts
  • Monocytes
  • Mitogen-Activated Protein Kinase 14
  • Mice