title: Runx1 dose-dependently regulates endochondral ossification during skeletal development and fracture healing.
abstract: Runx1 is expressed in skeletal elements, but its role in fracture repair has not been analyzed. We created mice with a hypomorphic Runx1 allele (Runx1(L148A) ) and generated Runx1(L148A/-) mice in which >50% of Runx1 activity was abrogated. Runx1(L148A/-) mice were viable but runted. Their growth plates had extended proliferating and hypertrophic zones, and the percentages of Sox9-, Runx2-, and Runx3-positive cells were decreased. Femoral fracture experiments revealed delayed cartilaginous callus formation, and the expression of chondrogenic markers was decreased. Conditional ablation of Runx1 in the mesenchymal progenitor cells of the limb with Prx1-Cre conferred no obvious limb phenotype; however, cartilaginous callus formation was delayed following fracture. Embryonic limb bud-derived mesenchymal cells showed delayed chondrogenesis when the Runx1 allele was deleted ex vivo with adenoviral-expressed Cre. Collectively, our data suggest that Runx1 is required for commitment and differentiation of chondroprogenitor cells into the chondrogenic lineage.
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06034, USA. soung@uchc.edu
authors.forename: Do Y
authors.initials: do Y
authors.lastname: Soung
authors.forename: Laleh
authors.initials: L
authors.lastname: Talebian
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Matheny
authors.forename: Rosa
authors.initials: R
authors.lastname: Guzzo
authors.forename: Maren E
authors.initials: ME
authors.lastname: Speck
authors.forename: Jay R
authors.initials: JR
authors.lastname: Lieberman
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Speck
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
mesh_terms: D000483:Alleles; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology*; D050676:Core Binding Factor Alpha 2 Subunit / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005091:Exons; D005260:Female; D017102:Fracture Healing; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D015675:Osteocalcin / Q000096:biosynthesis; D010641:Phenotype; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D015675:Osteocalcin