BMP9 stimulates joint regeneration at digit amputation wounds in mice

Nat Commun. 2019 Feb 5;10(1):424. doi: 10.1038/s41467-018-08278-4.

Abstract

A major goal of regenerative medicine is to stimulate tissue regeneration after traumatic injury. We previously discovered that treating digit amputation wounds with BMP2 in neonatal mice stimulates endochondral ossification to regenerate the stump bone. Here we show that treating the amputation wound with BMP9 stimulates regeneration of a synovial joint that forms an articulation with the stump bone. Regenerated structures include a skeletal element lined with articular cartilage and a synovial cavity, and we demonstrate that this response requires the Prg4 gene. Combining BMP2 and BMP9 treatments in sequence stimulates the regeneration of bone and joint. These studies provide evidence that treatment of growth factors can be used to engineer a regeneration response from a non-regenerating amputation wound.

Publication types

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

MeSH terms

  • Amputation, Surgical
  • Animals
  • Bone Regeneration
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / physiopathology
  • Female
  • Fingers / surgery*
  • Growth Differentiation Factor 2 / genetics
  • Growth Differentiation Factor 2 / metabolism*
  • Humans
  • Joints / metabolism
  • Joints / physiopathology*
  • Male
  • Mice
  • Mice, Knockout
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism
  • Proteoglycans / genetics
  • Proteoglycans / metabolism
  • Wound Healing
  • Wounds and Injuries / genetics
  • Wounds and Injuries / metabolism*
  • Wounds and Injuries / physiopathology

Substances

  • Gdf2 protein, mouse
  • Growth Differentiation Factor 2
  • Myelin Basic Protein
  • Prg4 protein, mouse
  • Proteoglycans