title: Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair.
abstract: Mice in which Cbl is unable to bind PI3K (YF mice) display increased bone volume due to enhanced bone formation and repressed bone resorption during normal bone homeostasis. We investigated the effects of disrupted Cbl-PI3K interaction on fracture healing to determine whether this interaction has an effect on bone repair. Mid-diaphyseal femoral fractures induced in wild type (WT) and YF mice were temporally evaluated via micro-computed tomography scans, biomechanical testing, histological and histomorphometric analyses. Imaging analyses revealed no change in soft callus formation, increased bony callus formation, and delayed callus remodeling in YF mice compared to WT mice. Histomorphometric analyses showed significantly increased osteoblast surface per bone surface and osteoclast numbers in the calluses of YF fractured mice, as well as increased incorporation of dynamic bone labels. Furthermore, using laser capture micro-dissection of the fracture callus we found that cells lacking Cbl-PI3K interaction have higher expression of Osterix, TRAP, and Cathepsin K. We also found increased expression of genes involved in propagating PI3K signaling in cells isolated from the YF fracture callus, suggesting that the lack of Cbl-PI3K interaction perhaps results in enhanced PI3K signaling, leading to increased bone formation, but delayed remodeling in the healing femora.
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Scanlon
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Do Yu
authors.initials: do Y
authors.lastname: Soung
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Naga Suresh
authors.initials: NS
authors.lastname: Adapala
authors.affiliation: Department of Mechanical Engineering, Boston University, Boston, MA, United States of America.
authors.forename: Elise
authors.initials: E
authors.lastname: Morgan
authors.affiliation: Center for Molecular Medicine, University of Connecticut Health Center, Farmington, CT, United States of America; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hansen
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, United States of America; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, United States of America; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, United States of America.
authors.forename: Archana
authors.initials: A
authors.lastname: Sanjay
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*
chemical_list: D050721:Proto-Oncogene Proteins c-cbl; D019869:Phosphatidylinositol 3-Kinases; C493849:Cbl protein, mouse