Hepatocyte growth factor and p38 promote osteogenic differentiation of human mesenchymal stem cells

Kristina K. Aenlle, Kevin M. Curtis, Bernard A. Roos, Guy Howard

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF) is a paracrine factor involved in organogenesis, tissue repair, and wound healing. We report here that HGF promotes osteogenic differentiation through the transcription of key osteogenic markers, including osteocalcin, osterix, and osteoprotegerin in human mesenchymal stem cells and is a necessary component for the establishment of osteoblast mineralization. Blocking endogenous HGF using PHA665752, a c-Met inhibitor (the HGF receptor), or an HGF-neutralizing antibody attenuates mineralization, and PHA665752 markedly reduced alkaline phosphatase activity. Moreover, we report that HGF promotion of osteogenic differentiation involves the rapid phosphorylation of p38 and differential regulation of its isoforms, p38α and p38β. Western blot analysis revealed a significantly increased level of p38α and p38β protein, and reverse transcription quantitative PCR revealed that HGF increased the transcriptional level of both p38α and p38β. Using small interfering RNA to reduce the transcription of p38α and p38β,we saw differential roles for p38α and p38β on the HGF-induced expression of key osteogenic markers. In summary, our data demonstrate the importance of p38 signaling in HGF regulation of osteogenic differentiation.

Original languageEnglish
Pages (from-to)722-730
Number of pages9
JournalMolecular Endocrinology
Volume28
Issue number5
DOIs
StatePublished - Jan 1 2014

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Hepatocyte Growth Factor
Mesenchymal Stromal Cells
Proto-Oncogene Proteins c-met
Osteoprotegerin
Organogenesis
Osteocalcin
Neutralizing Antibodies
Osteoblasts
Wound Healing
Small Interfering RNA
Reverse Transcription
Alkaline Phosphatase
Protein Isoforms
Western Blotting
Phosphorylation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Hepatocyte growth factor and p38 promote osteogenic differentiation of human mesenchymal stem cells. / Aenlle, Kristina K.; Curtis, Kevin M.; Roos, Bernard A.; Howard, Guy.

In: Molecular Endocrinology, Vol. 28, No. 5, 01.01.2014, p. 722-730.

Research output: Contribution to journalArticle

Aenlle, Kristina K. ; Curtis, Kevin M. ; Roos, Bernard A. ; Howard, Guy. / Hepatocyte growth factor and p38 promote osteogenic differentiation of human mesenchymal stem cells. In: Molecular Endocrinology. 2014 ; Vol. 28, No. 5. pp. 722-730.
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