Interleukin 17 inhibits myogenic and promotes osteogenic differentiation of C2C12 myoblasts by activating ERK1,2

Biochim Biophys Acta. 2012 Apr;1823(4):838-49. doi: 10.1016/j.bbamcr.2012.01.001. Epub 2012 Jan 17.


The present study evaluated the role of interleukin (IL) 17 in multilineage commitment of C2C12 myoblastic cells and investigated associated signaling pathways. The results concerning the effects on cell function showed that IL-17 inhibits the migration of C2C12 cells, while not affecting their proliferation. The data regarding the influence on differentiation demonstrated that IL-17 inhibits myogenic differentiation of C2C12 cells by down-regulating the myogenin mRNA level, myosin heavy chain expression and myotube formation, but promotes their osteogenic differentiation by up-regulating the Runt-related transcription factor 2 mRNA level, cyclooxygenase-2 expression and alkaline phosphatase activity. IL-17 exerted these effects by activating ERK1,2 mitogen activated protein kinase signaling pathway, which in turn regulated the expression of relevant genes and proteins to inhibit myogenic differentiation and induce osteogenic differentiation. Additional analysis showed that the induction of osteogenic differentiation by IL-17 is independent of BMP signaling. The results obtained demonstrate the potential of IL-17 not only to inhibit the myogenic differentiation of C2C12 myoblasts but also to convert their differentiation pathway into that of osteoblast lineage providing new insight into the capacities of IL-17 to modulate the differentiation commitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Enzyme Activation / drug effects
  • Interleukin-17 / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Models, Biological
  • Muscle Development / drug effects*
  • Myoblasts / cytology*
  • Myoblasts / drug effects
  • Myoblasts / enzymology
  • Osteogenesis / drug effects*
  • Receptors, Interleukin-17 / metabolism


  • Bone Morphogenetic Proteins
  • Interleukin-17
  • Receptors, Interleukin-17
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3