OR01-5 Osteoblast-specific Knockout of the Insulin-like Growth Factor I Receptor (IGF-IR) Gene Impairs Endochondral Bone Formation in Unstable Fracture Healing

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR01-Cell Specific GH & IGF-1 Signaling
Basic
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 12:30 PM
Room 134 (Moscone Center)
TAO WANG*1, Muriel Babey1, Yongmei Wang2, Candice Tahimic1, Frankie Fong1, Alicia Menendez1, Zhiqiang Cheng3 and Daniel D Bikle4
1Veterans Affairs Medical Center and University of California, san francisco, CA, 2UCSF, San Francisco, CA, 3Va Med Ctr UCSF, San Francisco, CA, 4VA Med Ctr 111N-UCSF, San Francisco, CA
Insulin-like Growth Factor I (IGF-I) signaling plays an important role in osteoblastic differentiation, cell proliferation and the synthesis of collagen and other matrix  proteins . Mice with osteoblast-specific loss of the IGF-1 receptor (IGF-IR) have decreased osteoblast proliferation, increased apoptosis and reduced bone both trabecular and cortical. We tested the hypothesis that loss of IGF-1R results in decreased bone formation and impaired healing following fracture.  To determine the role of IGF-IR in fracture healing, a closed tibial fracture was induced in female IGF-I flox/flox / Collagen 2.3kb driven Cre (IGF-IR KO) and IGF-I flox/flox (CON) mice aged 12 weeks. The tibial fracture callus was evaluated by micro CT, bone histomorphometry  and gene expression 10, 21, and 28d after fracture. Bone formation was assessed with two flurochrome labels prior to euthanasia. The results show that osteoblast-specific deletion of IGF-IR results in decreased bone formation, bone remodeling, and mineralizing process, as well as delayed cartilage turnover in IGF-IR KO mice. These studies identify an important role of IGF-I signaling during fracture healing, suggesting that loss of IGF-IR in osteoblasts results in delayed chondrocyte maturation and conversion into bone resulting in delayed union. Therefore, enhancing IGF-I signaling may provide a means to enhance endochondral bone formation resulting in improved  fracture healing.

Nothing to Disclose: TW, MB, YW, CT, FF, AM, ZC, DDB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm