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

Overview
Specialty Biochemistry
Date 2017 Oct 24
PMID 29057206
Citations 27
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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: ERK and p38 MAP kinases 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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References
1.
Labrador J, Azcoitia V, Tuckermann J, Lin C, Olaso E, Manes S . The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism. EMBO Rep. 2001; 2(5):446-52. PMC: 1083888. DOI: 10.1093/embo-reports/kve094. View

2.
Luu Y, Capilla E, Rosen C, Gilsanz V, Pessin J, Judex S . Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res. 2008; 24(1):50-61. PMC: 2689082. DOI: 10.1359/jbmr.080817. View

3.
Yao Y, Li W, Wu J, Germann U, Su M, Kuida K . Extracellular signal-regulated kinase 2 is necessary for mesoderm differentiation. Proc Natl Acad Sci U S A. 2003; 100(22):12759-64. PMC: 240691. DOI: 10.1073/pnas.2134254100. View

4.
Tanabe Y, Koga M, Saito M, Matsunaga Y, Nakayama K . Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPARgamma2. J Cell Sci. 2004; 117(Pt 16):3605-14. DOI: 10.1242/jcs.01207. View

5.
Ge C, Xiao G, Jiang D, Yang Q, Hatch N, Roca H . Identification and functional characterization of ERK/MAPK phosphorylation sites in the Runx2 transcription factor. J Biol Chem. 2009; 284(47):32533-43. PMC: 2781667. DOI: 10.1074/jbc.M109.040980. View