title: Sclerostin deficient mice rapidly heal bone defects by activating β-catenin and increasing intramembranous ossification.
abstract: We investigated the influence of the osteocyte protein, sclerostin, on fracture healing by examining the dynamics and mechanisms of repair of single-cortex, stabilized femoral defects in sclerostin knockout (Sost(-/-); KO) and sclerostin wild-type (Sost(+/+); WT) mice. Fourteen days following generation of bone defects, Sost KO mice had significantly more bone in the healing defect than WT mice. The increase in regenerating bone was due to an increase in the thickness of trabecularized spicules, osteoblast numbers and surfaces within the defect. Enhanced healing of bone defects in Sost KO mice was associated with significantly more activated β-catenin expression than observed in WT mice. The findings were similar to those observed in Axin2(-/-) mice, in which β-catenin signaling is known to be enhanced to facilitate bone regeneration. Taken together, these data indicate that enhanced β-catenin signaling is present in Sost(-/-) mice that demonstrate accelerated healing of bone defects, suggesting that modulation of β-catenin signaling in bone could be used to promote fracture repair.
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, 200 1st St., Southwest, Rochester, MN 55905, USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: McGee-Lawrence
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Ryan
authors.forename: Lomeli R
authors.initials: LR
authors.lastname: Carpio
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D017102:Fracture Healing / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics*; D015398:Signal Transduction; D051176:beta Catenin / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C111729:Axin2 protein, mouse; C495267:CTNNB1 protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse; D051176:beta Catenin
keywords: Fracture healing; Intramembranous ossification; Osteoblast; Sclerostin; Wnt; β-Catenin