2010
DOI: 10.1172/jci42285
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The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice

Abstract: Nearly every extracellular ligand that has been found to play a role in regulating bone biology acts, at least in part, through MAPK pathways. Nevertheless, much remains to be learned about the contribution of MAPKs to osteoblast biology in vivo. Here we report that the p38 MAPK pathway is required for normal skeletogenesis in mice, as mice with deletion of any of the MAPK pathway member-encoding genes MAPK kinase 3 (Mkk3), Mkk6, p38a, or p38b displayed profoundly reduced bone mass secondary to defective osteo… Show more

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Cited by 360 publications
(391 citation statements)
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“…(46) Phosphorylation of Ser17, 261, and 298 by p38 MAP kinase promotes the association of Runx2 with its coactivator, CREB-binding protein (CBP). (47) In addition, Ser22 phosphorylated by PKCd and Thr341 phosphorylated by PKA are required for, respectively, FGF2 and PTH-induced Runx2 activation and osteoblastic differentiation. (48,49) Contrarily, the phosphorylation of Ser369, 373, and 377 by GSK3b was shown to inhibit Runx2 transcriptional activity.…”
Section: Discussionmentioning
confidence: 99%
“…(46) Phosphorylation of Ser17, 261, and 298 by p38 MAP kinase promotes the association of Runx2 with its coactivator, CREB-binding protein (CBP). (47) In addition, Ser22 phosphorylated by PKCd and Thr341 phosphorylated by PKA are required for, respectively, FGF2 and PTH-induced Runx2 activation and osteoblastic differentiation. (48,49) Contrarily, the phosphorylation of Ser369, 373, and 377 by GSK3b was shown to inhibit Runx2 transcriptional activity.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, several reports have also indicated that the p38 pathway regulates the expression and activation of critical transcription factors implicated in osteoblastogenesis, i.e., Dlx5, Runx2, and Osx [5,[10][11][12].…”
Section: Introductionmentioning
confidence: 99%
“…More recently, an in vivo investigation has highlighted the physiological role of TGF-b-activated kinase 1 (TAK1) in osteoblastogenesis and bone formation [12]. TAK1 is a MAP3 K acting downstream of BMP and TGF-b receptors.…”
Section: Introductionmentioning
confidence: 99%
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