title: Accelerated hypertrophic chondrocyte kinetics in GDF-7 deficient murine tibial growth plates.
abstract: The Growth/Differentiation Factors (GDFs) are a subgroup of the Bone Morphogenetic Proteins (BMPs) well known for their role in joint formation and chondrogenesis. Mice deficient in one of these signaling molecules, GDF-5, have recently been shown to exhibit a decreased rate of endochondral bone growth in the proximal tibia due to a significantly longer hypertrophic phase duration. GDF-7 is a related family member, which exhibits a high degree of sequence identity with GDF-5. The purpose of the present study was to determine whether GDF-7 deficiency also alters the endochondral bone growth rate in mice and, if so, how this is achieved. Stereologic and cell kinetic parameters in proximal tibial growth plates from 5-week-old female GDF-7 -/- mice and wild type control littermates were examined. GDF-7 deficiency resulted in a statistically significant increase in growth rate (+26%; p = 0.0084) and rate of cell loss at the chondrosseous junction (+25%; p = 0.0217). Cells from GDF-7 deficient mice also exhibited a significantly shorter hypertrophic phase duration compared to wild type controls (-27%; p = 0.0326). These data demonstrate that, in the absence of GDF-7, the rate of endochondral bone growth is affected through the modulation of hypertrophic phase duration in growth plate chondrocytes. These findings further support a growing body of evidence implicating the GDFs in the formation, maturation, and maintenance of healthy cartilage.
authors.affiliation: Picker Engineering Program, Smith College, 51 College Lane, Northampton, Massachusetts 01063, USA. bmikic@email.smith.edu
authors.forename: Borjana
authors.initials: B
authors.lastname: Mikic
authors.forename: Maria P
authors.initials: MP
authors.lastname: Ferreira
authors.forename: Todd C
authors.initials: TC
authors.lastname: Battaglia
authors.forename: Ernst B
authors.initials: EB
authors.lastname: Hunziker
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000172:deficiency*; D019902:Chondrocytes / Q000502:physiology*; D005260:Female; D055412:Growth Differentiation Factors; D006132:Growth Plate / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D013977:Tibia / Q000254:growth & development*
chemical_list: D019485:Bone Morphogenetic Proteins; C499471:Gdf7 protein, mouse; D055412:Growth Differentiation Factors