IGF-1 and Integrin signaling pathways cooperatively modulate the response of osteoblastic cells to IGF-1 and shear stress

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 389-405-Signaling Originating from Membrane Receptors
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-394
Candice GT Tahimic*1, Roger K Long2, Takuo Kubota3, Alicia T Menendez1, Chak Fong4, Yongmei Wang5 and Daniel D Bikle6
1VA Medical Center / University of California, San Francisco, CA, 2University of California, San Francisco, CA, 3Osaka University, Osaka, Japan, 4University of California, San Francisco, VA Medical Center, San Francisco, CA, 5University of California, San Francisco, VA Medical Center, San Francisco, CA, 6UCSF, San Francisco, CA
Physical activity results in increased bone formation, as demonstrated by the higher bone mass in the playing arm of long-term tennis players versus their non-dominant arm. On the other hand, skeletal unloading in rats by hindlimb elevation results in bone loss due to reduced bone formation consequent to impaired osteoblast proliferation and increased apoptosis. A key question we intend to address is how the skeleton senses mechanical forces and translates these stimuli into signals that regulate osteogenic proliferation and differentiation to ultimately result in bone formation. We propose that one of the mechanisms by which this is achieved is through the interplay of the IGF-I and integrin signaling pathways. Integrins are membrane-bound proteins that associate with specific extracellular matrix (ECM) molecules and are thought to play a role in cell adhesion and mechanosensing. IGF-1 and integrin signaling pathways share common downstream effectors such as Akt and MAPK. In this current study, we show that the response of the human osteoblastic cell line HOS to pulsatile fluid flow (PFF) is modulated by IGF-1 signaling. Specifically, pretreatment with a neutralizing antibody against IGF-1 results in a blunted Akt and Erk phosphorylation response to PFF. We also demonstrate that inhibition of proteins associated with the Integrin pathway results in a diminished Akt and MAPK phosphorylation response to IGF-1. These findings suggest that IGF-1 and Integrin signaling pathways cooperatively modulate the response of osteoblastic cells to anabolic factors such as IGF-1 and mechanical stimulation. We are currently investigating the IGF-1 and Integrin-dependent signaling events upstream of Akt and Erk activation using co-immunoprecipitation studies and biomolecular fluorescence complementation.

Nothing to Disclose: CGT, RKL, TK, ATM, CF, YW, DDB

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