HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 20, 20163-20170, May 20, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/20/20163    most recent M501460200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kapur, S. Articles by Lau, K.-H. W. Search for Related Content PubMed PubMed Citation Articles by Kapur, S. Articles by Lau, K.-H. W. Social Bookmarking                      What's this?

Fluid Shear Stress Synergizes with Insulin-like Growth Factor-I (IGF-I) on Osteoblast Proliferation through Integrin-dependent Activation of IGF-I Mitogenic Signaling Pathway^*

Sonia Kapur, Subburaman Mohan, David J. Baylink, and K.-H. William Lau¶

From the Musculoskeletal Disease Center, Jerry L. Pettis Memorial Veterans Affairs Medical Center, and Departments of Medicine and Biochemistry, Loma Linda University, Loma Linda, California 92357

This study tested the hypothesis that shear stress interacts with the insulin-like growth factor-I (IGF-I) pathway to stimulate osteoblast proliferation. Human TE85 osteosarcoma cells were subjected to a steady shear stress of 20 dynes/cm² for 30 min followed by 24-h incubation with IGF-I (0–50 ng/ml). IGF-I increased proliferation dose-dependently (1.5–2.5-fold). Shear stress alone increased proliferation by 70%. The combination of shear stress and IGF-I stimulated proliferation (3.5- to 5.5-fold) much greater than the additive effects of each treatment alone, indicating a synergistic interaction. IGF-I dose-dependently increased the phosphorylation level of Erk1/2 by 1.2–5.3-fold and that of IGF-I receptor (IGF-IR) by 2–4-fold. Shear stress alone increased Erk1/2 and IGF-IR phosphorylation by 2-fold each. The combination treatment also resulted in synergistic enhancements in both Erk1/2 and IGF-IR phosphorylation (up to 12- and 8-fold, respectively). Shear stress altered IGF-IR binding only slightly, suggesting that the synergy occurred primarily at the post-ligand binding level. Recent studies have implicated a role for integrin in the regulation of IGF-IR phosphorylation and IGF-I signaling. To test whether the synergy involves integrin-dependent mechanisms, the effect of echistatin (a disintegrin) on proliferation in response to shear stress ± IGF-I was measured. Echistatin reduced basal proliferation by 60% and the shear stress-induced mitogenic response by 20%. It completely abolished the mitogenic effect of IGF-I and that of the combination treatment. Shear stress also significantly reduced the amounts of co-immunoprecipitated SHP-2 and -1 with IGF-IR, suggesting that the synergy between shear stress and IGF-I in osteoblast proliferation involves integrin-dependent recruitment of SHP-2 and -1 away from IGF-IR.

Received for publication, February 8, 2005 , and in revised form, March 14, 2005.

^* This work was supported in part by a special appropriation to the Musculoskeletal Disease Center, Jerry L. Pettis Memorial Veterans Administration Medical Center, and by a merit review provided by the Office of Research and Development, Medical Research Service, Department of Veteran Affairs and also in part by Assistance Award DAMD17-01-1-0744.

^¶ To whom correspondence should be addressed: Musculoskeletal Disease Ctr. (151), Jerry L. Pettis Memorial Veterans Affairs Medical Ctr., 11201 Benton St., Loma Linda, CA 92357. Tel.: 909-825-7084 (ext. 2836); Fax: 909-796-1680; E-mail: William.Lau{at}med.va.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. K. Saxon, A. G. Robling, A. B. Castillo, S. Mohan, and C. H. Turner The skeletal responsiveness to mechanical loading is enhanced in mice with a null mutation in estrogen receptor-beta Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E484 - E491. [Abstract] [Full Text] [PDF]

				B. M. Boudignon, D. D. Bikle, P. Kurimoto, H. Elalieh, S. Nishida, Y. Wang, A. Burghardt, S. Majumdar, B. E. Orwoll, C. Rosen, et al. Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading J Appl Physiol, July 1, 2007; 103(1): 125 - 131. [Abstract] [Full Text] [PDF]

				K.-H. W. Lau, S. Kapur, C. Kesavan, and D. J. Baylink Up-regulation of the Wnt, Estrogen Receptor, Insulin-like Growth Factor-I, and Bone Morphogenetic Protein Pathways in C57BL/6J Osteoblasts as Opposed to C3H/HeJ Osteoblasts in Part Contributes to the Differential Anabolic Response to Fluid Shear J. Biol. Chem., April 7, 2006; 281(14): 9576 - 9588. [Abstract] [Full Text] [PDF]

				L. A. Maile, W. H. Busby, K. Sitko, B. E. Capps, T. Sergent, J. Badley-Clarke, Y. Ling, and D. R. Clemmons The Heparin Binding Domain of Vitronectin Is the Region that Is Required to Enhance Insulin-Like Growth Factor-I Signaling Mol. Endocrinol., April 1, 2006; 20(4): 881 - 892. [Abstract] [Full Text] [PDF]