Bone morphogenetic proteins and their antagonists: current and emerging clinical uses

Br J Pharmacol. 2014 Aug;171(15):3620-32. doi: 10.1111/bph.12724.

Abstract

Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily of secreted cysteine knot proteins that includes TGFβ1, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralized bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes, including limb, kidney, skin, hair and neuronal development, as well as maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment of several pathologies, including bone disorders, kidney and lung fibrosis, and cancer. This review will summarize current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMPs as pharmacological agents for the treatment of bone repair and tissue fibrosis in patients.

Keywords: bone morphogenetic protein; fibrosis; fracture; gremlin; inhibitors; scarring; skeleton.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Development
  • Bone Morphogenetic Proteins* / antagonists & inhibitors
  • Bone Morphogenetic Proteins* / metabolism
  • Bone Morphogenetic Proteins* / therapeutic use
  • Bone Regeneration / drug effects
  • Fibrosis
  • Humans
  • Recombinant Proteins / therapeutic use
  • Signal Transduction
  • Smad Proteins / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Recombinant Proteins
  • Smad Proteins