P38 MAPK Signaling in Osteoblast Differentiation

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2016 May 21

PMID 27200351

Citations 155

Authors

Eddie Rodriguez-Carballo

Beatriz Gamez

Francesc Ventura

Affiliations

Soon will be listed here.

Abstract

The skeleton is a highly dynamic tissue whose structure relies on the balance between bone deposition and resorption. This equilibrium, which depends on osteoblast and osteoclast functions, is controlled by multiple factors that can be modulated post-translationally. Some of the modulators are Mitogen-activated kinases (MAPKs), whose role has been studied in vivo and in vitro. p38-MAPK modifies the transactivation ability of some key transcription factors in chondrocytes, osteoblasts and osteoclasts, which affects their differentiation and function. Several commercially available inhibitors have helped to determine p38 action on these processes. Although it is frequently mentioned in the literature, this chemical approach is not always as accurate as it should be. Conditional knockouts are a useful genetic tool that could unravel the role of p38 in shaping the skeleton. In this review, we will summarize the state of the art on p38 activity during osteoblast differentiation and function, and emphasize the triggers of this MAPK.

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References

Gamell C, Osses N, Bartrons R, Ruckle T, Camps M, Rosa J . BMP2 induction of actin cytoskeleton reorganization and cell migration requires PI3-kinase and Cdc42 activity. J Cell Sci. 2008; 121(Pt 23):3960-70. DOI: 10.1242/jcs.031286. View

Wang X, Tokuda H, Hatakeyama D, Hirade K, Niwa M, Ito H . Mechanism of simvastatin on induction of heat shock protein in osteoblasts. Arch Biochem Biophys. 2003; 415(1):6-13. DOI: 10.1016/s0003-9861(03)00213-3. View

Liu L, Channavajhala P, Rao V, Moutsatsos I, Wu L, Zhang Y . Proteomic characterization of the dynamic KSR-2 interactome, a signaling scaffold complex in MAPK pathway. Biochim Biophys Acta. 2009; 1794(10):1485-95. DOI: 10.1016/j.bbapap.2009.06.016. View

Yuan L, Sakamoto N, Song G, Sato M . Migration of human mesenchymal stem cells under low shear stress mediated by mitogen-activated protein kinase signaling. Stem Cells Dev. 2012; 21(13):2520-30. DOI: 10.1089/scd.2012.0010. View

Patil C, Zhu X, Rossa Jr C, Kim Y, Kirkwood K . p38 MAPK regulates IL-1beta induced IL-6 expression through mRNA stability in osteoblasts. Immunol Invest. 2004; 33(2):213-33. PMC: 1201547. DOI: 10.1081/imm-120034231. View

Cervenka I, Wolf J, Masek J, Krejci P, Wilcox W, Kozubik A . Mitogen-activated protein kinases promote WNT/beta-catenin signaling via phosphorylation of LRP6. Mol Cell Biol. 2010; 31(1):179-89. PMC: 3019858. DOI: 10.1128/MCB.00550-10. View

Hata K, Nishimura R, Ikeda F, Yamashita K, Matsubara T, Nokubi T . Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis. Mol Biol Cell. 2003; 14(2):545-55. PMC: 149991. DOI: 10.1091/mbc.e02-06-0356. View

Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N . The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol. 2008; 10(10):1199-207. DOI: 10.1038/ncb1780. View

OCallaghan C, Fanning L, Houston A, Barry O . Loss of p38δ mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth. Int J Oncol. 2013; 43(2):405-15. PMC: 3775579. DOI: 10.3892/ijo.2013.1968. View

10.

Feng M, Tian L, Gan L, Liu Z, Sun C . Mark4 promotes adipogenesis and triggers apoptosis in 3T3-L1 adipocytes by activating JNK1 and inhibiting p38MAPK pathways. Biol Cell. 2014; 106(9):294-307. DOI: 10.1111/boc.201400004. View

11.

Kocic J, Santibanez J, Krstic A, Mojsilovic S, Ilic V, Bugarski D . Interleukin-17 modulates myoblast cell migration by inhibiting urokinase type plasminogen activator expression through p38 mitogen-activated protein kinase. Int J Biochem Cell Biol. 2012; 45(2):464-75. DOI: 10.1016/j.biocel.2012.11.010. View

12.

Minamitani C, Otsuka T, Takai S, Matsushima-Nishiwaki R, Adachi S, Hanai Y . Involvement of Rho-kinase in prostaglandin F2alpha-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts. Mol Cell Endocrinol. 2008; 291(1-2):27-32. DOI: 10.1016/j.mce.2008.05.011. View

13.

Lee H, Kim S, Kim A, Lee E, Choi J, Kim J . Adiponectin stimulates osteoblast differentiation through induction of COX2 in mesenchymal progenitor cells. Stem Cells. 2009; 27(9):2254-62. DOI: 10.1002/stem.144. View

14.

Kim I, Song Y, Hwang S . Osteogenic responses of human mesenchymal stromal cells to static stretch. J Dent Res. 2010; 89(10):1129-34. DOI: 10.1177/0022034510375283. View

15.

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

16.

Fu X, Han B, Cai S, Lei Y, Sun T, Sheng Z . Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-alpha and its possible role in wound healing. Wound Repair Regen. 2009; 17(2):185-91. DOI: 10.1111/j.1524-475X.2009.00454.x. View

17.

Fuentealba L, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera E . Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell. 2007; 131(5):980-93. PMC: 2200633. DOI: 10.1016/j.cell.2007.09.027. View

18.

Long F . Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol. 2011; 13(1):27-38. DOI: 10.1038/nrm3254. View

19.

Yumoto H, Hirao K, Tominaga T, Bando N, Takahashi K, Matsuo T . Electromagnetic wave irradiation promotes osteoblastic cell proliferation and up-regulates growth factors via activation of the ERK1/2 and p38 MAPK pathways. Cell Physiol Biochem. 2015; 35(2):601-15. DOI: 10.1159/000369722. View

20.

Rey A, Manen D, Rizzoli R, Ferrari S, Caverzasio J . Evidences for a role of p38 MAP kinase in the stimulation of alkaline phosphatase and matrix mineralization induced by parathyroid hormone in osteoblastic cells. Bone. 2007; 41(1):59-67. DOI: 10.1016/j.bone.2007.02.031. View