BMP10 positively regulates myogenic differentiation in C2C12 myoblasts via the Smad 1/5/8 signaling pathway

Mol Cell Biochem. 2021 May;476(5):2085-2097. doi: 10.1007/s11010-021-04064-x. Epub 2021 Jan 30.

Abstract

BMP10 plays an essential role in regulating cardiac growth, chamber maturation, and maintaining normal expressions of several key cardiogenic factors; however, other functional roles of BMP10 in muscle remain unexplored. This study therefore undertook to investigate the roles of BMP10 in muscle physiology, using mouse-derived C2C12 myoblasts. Bmp10 silencing prevented a number of biological processes such as myogenic differentiation, glucose uptake, and lipid catabolism, whereas exogenous induction of BMP10 in C2C12 cells significantly stimulated the expression of proteins and genes involved in these processes, as well as mitochondrial biogenesis and thermogenesis, resulting in reduced lipid accumulation. A mechanistic study revealed that BMP10 stimulates myogenesis mainly via the Smad 1/5/8 signaling pathway. In conclusion, our data unveiled a previously unknown mechanism in the regulation of lipid metabolisms by BMP10 in muscle cells and identified its significant roles in systemic metabolic homeostasis, shedding light on BMP10 as a pharmacotherapeutic target to treat metabolic disorders.

Keywords: BMP10; C2C12 cells; Lipid metabolism; Myogenesis.

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Mice
  • Muscle Development*
  • Myoblasts / metabolism*
  • Signal Transduction*
  • Smad1 Protein / genetics
  • Smad1 Protein / metabolism*
  • Smad5 Protein / genetics
  • Smad5 Protein / metabolism*
  • Smad8 Protein / genetics
  • Smad8 Protein / metabolism*

Substances

  • Bmp10 protein, mouse
  • Bone Morphogenetic Proteins
  • Smad1 Protein
  • Smad1 protein, mouse
  • Smad5 Protein
  • Smad5 protein, mouse
  • Smad8 Protein
  • Smad9 protein, mouse