GDF8 inhibits bone formation and promotes bone resorption in mice

Clin Exp Pharmacol Physiol. 2017 Apr;44(4):500-508. doi: 10.1111/1440-1681.12728.

Abstract

Growth Differentiation Factor 8 (GDF8), also called myostatin, is a member of the transforming growth factor (TGF)-β super-family. As a negative regulator of skeletal muscle growth, GDF8 is also associated with bone metabolism. However, the function of GDF8 in bone metabolism is not fully understood. Our study aimed to investigate the role of GDF8 in bone metabolism, both in vitro and in vivo. Our results showed that GDF8 had a negative regulatory effect on primary mouse osteoblasts, and promoted receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro. Intraperitoneal injection of recombinant GDF8 repressed bone formation and accelerated bone resorption in mice. Furthermore, treatment of aged mice with a GDF8 neutralizing antibody stimulated new bone formation and prevented bone resorption. Thus, our study showed that GDF8 plays a significant regulatory role in bone formation and bone resorption, thus providing a potential therapeutic pathway for osteoporosis.

Keywords: GDF8; neutralizing antibody; osteoblast; osteoclastogenesis; osteoporosis.

MeSH terms

  • Animals
  • Bone Resorption / pathology
  • Bone Resorption / physiopathology*
  • Calcification, Physiologic / drug effects
  • Cell Differentiation / drug effects
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Myostatin / metabolism*
  • Osteoblasts / drug effects
  • Osteoblasts / pathology
  • Osteogenesis* / drug effects
  • RANK Ligand / pharmacology

Substances

  • Myostatin
  • RANK Ligand

Associated data

  • GENBANK/NM_001146038
  • GENBANK/NM_130458
  • GENBANK/NM_016791
  • GENBANK/NM_007393