Multiple effects of GDF-5 deficiency on skeletal tissues: implications for therapeutic bioengineering

Ann Biomed Eng. 2004 Mar;32(3):466-76. doi: 10.1023/b:abme.0000017549.57126.51.


The growth/differentiation factors (GDFs) are a subfamily of the highly conserved group of bone morphogenetic protein (BMP) signaling molecules known to play a diverse set of roles in the skeletal system. GDFs 5, 6, and 7 in particular have been grouped together on the basis of the high degree of amino acid sequence homology in the C-terminal signaling region of these proteins. The existence of several naturally occurring and engineered mouse models with functional null mutations in these GDFs has led to a variety of investigations into the effects of GDF deficiency on skeletal tissues and processes. The best characterized of these models to date is the GDF-5-deficient brachypod (bp) mouse. In this paper, a comprehensive review of the studies performed on the bp mouse is provided in an effort to elucidate implications for potential therapeutic bioengineering applications using GDF-5. On the basis of the available evidence to date, GDF-5 may hold promise as a possible therapeutic agent for applications involving tendon/ligament repair as well as perhaps intervertebral disk degeneration, cartilage repair, and bone augmentation, although further detailed interventional studies will be required to investigate these potential applications.

Publication types

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

MeSH terms

  • Animals
  • Biomedical Engineering / methods
  • Bone Morphogenetic Proteins / deficiency*
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / therapeutic use*
  • Bone and Bones / metabolism*
  • Cartilage, Articular / metabolism*
  • Disease Models, Animal
  • Growth Differentiation Factor 5
  • Humans
  • Limb Deformities, Congenital / metabolism*
  • Mice
  • Mice, Knockout
  • Skin / metabolism*
  • Tendons / metabolism*
  • Tissue Engineering


  • Bone Morphogenetic Proteins
  • GDF5 protein, human
  • Gdf5 protein, mouse
  • Growth Differentiation Factor 5