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Control of the Osteoblast Lineage by Mitogen-Activated Protein Kinase Signaling

  • Molecular Biology of Skeletal Development (T Bellido, Section Editor)
  • Published:
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Abstract

Purpose of the Review

This review will provide a timely assessment of MAP kinase actions in bone development and homeostasis with particular emphasis on transcriptional control of the osteoblast lineage.

Recent Findings

Extracellular signal-regulated kinase (ERK) and p38 MAP kinase function as transducers of signals initiated by the extracellular matrix, mechanical loading, TGF-β, BMPs, and FGF2. MAPK signals may also affect and/or interact with other important pathways such as WNT and HIPPO. ERK and p38 MAP kinase pathways phosphorylate specific osteogenic transcription factors including RUNX2, Osterix, ATF4, and DLX5. For RUNX2, phosphorylation at specific serine residues initiates epigenetic changes in chromatin necessary for decondensation and increased transcription. MAPK also suppresses marrow adipogenesis by phosphorylating and inhibiting PPARγ, which may explain the well-known relationship between reduced skeletal loading and marrow fat accumulation.

Summary

MAPKs transduce signals from the extracellular environment to the nucleus allowing bone cells to respond to changes in hormonal/growth factor signaling and mechanical loading, thereby optimizing bone structure to meet physiological and mechanical needs of the body.

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Authors and Affiliations

  1. Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, 48109-1078, USA

    Renny T. Franceschi

  2. Department of Biological Chemistry, University of Michigan School of Medicine, Ann Arbor, MI, 48109-1078, USA

    Renny T. Franceschi & Chunxi Ge

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  1. Renny T. Franceschi
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  2. Chunxi Ge
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Correspondence to Renny T. Franceschi.

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This article is part of the Topical Collection on Molecular Biology of Skeletal Development

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Franceschi, R.T., Ge, C. Control of the Osteoblast Lineage by Mitogen-Activated Protein Kinase Signaling. Curr Mol Bio Rep 3, 122–132 (2017). https://doi.org/10.1007/s40610-017-0059-5

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