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Inhibition of PI3K/p70 S6K and p38 MAPK cascades increases osteoblastic differentiation induced by BMP-2

Francesc Viñals1, Teresa López-Rovira, Jose Luis Rosa

  • 1Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, C/Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Spain.

FEBS Letters
|January 5, 2002
PubMed

Insights

Bone morphogenetic proteins (BMPs) trigger osteogenic differentiation in C2C12 cells. The study reveals that PI3K/p70 S6K and p38 MAPK pathways negatively regulate this osteogenic process.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Bone morphogenetic proteins (BMPs) are crucial for bone formation and osteogenic differentiation.
  • C2C12 myoblasts serve as a model system to study cellular differentiation.
  • Signaling pathways like PI3K/p70 S6K and p38 MAPK are implicated in various cellular processes, including differentiation.

Purpose of the Study:

  • To investigate the role of phosphatidylinositol 3-kinase/p70 S6 kinase (PI3K/p70 S6K) and p38 mitogen-activated protein kinase (p38 MAPK) signaling cascades in BMP-2-induced osteogenic differentiation.
  • To determine the effect of inhibiting these pathways on osteogenic marker expression.

Main Methods:

  • Utilized C2C12 myoblast cell line.
  • Stimulated cells with Bone morphogenetic protein-2 (BMP-2).
  • Administered selective inhibitors for PI3K/p70 S6K (Ly294002, rapamycin) and p38 MAPK (SB203580) pathways.
  • Assessed expression of osteogenic markers like Cbfa1, alkaline phosphatase, and osteocalcin.

Main Results:

  • BMP-2 transiently stimulated PI3K/p70 S6K and p38 MAPK pathways, with no effect on p42/p44 MAPK (Erks).
  • Inhibitors of p38 MAPK and PI3K/p70 S6K did not block BMP-2-induced osteoblast differentiation.
  • These inhibitors potentiated the expression of late osteogenic markers, including alkaline phosphatase activity and osteocalcin.

Conclusions:

  • The PI3K/p70 S6K and p38 MAPK signaling cascades play a negative regulatory role in BMP-2-induced osteogenic differentiation of C2C12 cells.
  • These findings contrast with their known positive roles in myogenic differentiation.
  • Targeting these pathways could offer novel strategies for enhancing osteogenesis.

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