Multiple effects of GDF-5 deficiency on skeletal tissues: implications for therapeutic bioengineering.
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.
Mikic
Borjana
B
Picker Engineering Program, Smith College, Northampton, MA 01063, USA. bmikic@email.smith.edu
D000818:Animals; D001698:Biomedical Engineering / Q000379:methods; D019485:Bone Morphogenetic Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D001842:Bone and Bones / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D004195:Disease Models, Animal; D055428:Growth Differentiation Factor 5; D006801:Humans; D017880:Limb Deformities, Congenital / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012867:Skin / Q000378:metabolism*; D013710:Tendons / Q000378:metabolism*; D023822:Tissue Engineering
D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5