Role of Cbl-PI3K interaction during skeletal remodeling in a murine model of bone repair

Vanessa Scanlon, Do Yu Soung, Naga Suresh Adapala, Elise Morgan, Marc F. Hansen, Hicham Drissi, Archana Sanjay

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6 Scopus citations

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 toWT 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.

Original languageEnglish (US)
Article numbere0138194
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 22 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Scanlon, V., Soung, D. Y., Adapala, N. S., Morgan, E., Hansen, M. F., Drissi, H., & Sanjay, A. (2015). Role of Cbl-PI3K interaction during skeletal remodeling in a murine model of bone repair. PLoS One, 10(9), [e0138194]. https://doi.org/10.1371/journal.pone.0138194