Erk1 positively regulates osteoclast differentiation and bone resorptive activity

Yongzheng He, Karl Staser, Steven D. Rhodes, Yaling Liu, Xiaohua Wu, Su Jung Park, Jin Yuan, Xianlin Yang, Xiaohong Li, Li Jiang, Shi Chen, Feng Chun Yang

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The extracellular signal-regulated kinases (ERK1 and 2) are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1 -/- bone marrow mononuclear cells (BMMNCs) demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2 -/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

Original languageEnglish
Article numbere24780
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 22 2011

Fingerprint

osteoclasts
Osteoclasts
Bone
bones
Bone and Bones
mitogen-activated protein kinase
Bone Marrow Cells
bone marrow
Noonan Syndrome
cells
Inborn Genetic Diseases
Neurofibromatosis 1
Macrophage Colony-Stimulating Factor
skeletal development
Macrophages
Mitogen-Activated Protein Kinase 1
Bone Development
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
bone density

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

He, Y., Staser, K., Rhodes, S. D., Liu, Y., Wu, X., Park, S. J., ... Yang, F. C. (2011). Erk1 positively regulates osteoclast differentiation and bone resorptive activity. PLoS One, 6(9), [e24780]. https://doi.org/10.1371/journal.pone.0024780

Erk1 positively regulates osteoclast differentiation and bone resorptive activity. / He, Yongzheng; Staser, Karl; Rhodes, Steven D.; Liu, Yaling; Wu, Xiaohua; Park, Su Jung; Yuan, Jin; Yang, Xianlin; Li, Xiaohong; Jiang, Li; Chen, Shi; Yang, Feng Chun.

In: PLoS One, Vol. 6, No. 9, e24780, 22.09.2011.

Research output: Contribution to journalArticle

He, Y, Staser, K, Rhodes, SD, Liu, Y, Wu, X, Park, SJ, Yuan, J, Yang, X, Li, X, Jiang, L, Chen, S & Yang, FC 2011, 'Erk1 positively regulates osteoclast differentiation and bone resorptive activity', PLoS One, vol. 6, no. 9, e24780. https://doi.org/10.1371/journal.pone.0024780
He, Yongzheng ; Staser, Karl ; Rhodes, Steven D. ; Liu, Yaling ; Wu, Xiaohua ; Park, Su Jung ; Yuan, Jin ; Yang, Xianlin ; Li, Xiaohong ; Jiang, Li ; Chen, Shi ; Yang, Feng Chun. / Erk1 positively regulates osteoclast differentiation and bone resorptive activity. In: PLoS One. 2011 ; Vol. 6, No. 9.
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