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The multi-functional role of insulin-like growth factor binding proteins in bone

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Abstract

The insulin-like growth factor (IGF) system is an important regulator of bone formation. The IGFs (IGF-I and IGF-II) are the most abundant growth factors produced by bone, and are regulated by their six high affinity binding proteins (IGFBPs). The IGFBPs are produced by osteoblasts and are responsible for transporting the IGFs and extending their half-lives. In general, IGFBP-1, -2, -4, and -6 inhibit and IGFBP-3 and –5 stimulate osteoblast function. IGFBP-4 and -5 are the most abundant IGFBPs produced by osteoblasts, and therefore they are the primary focus of this review. IGFBP-5 is an important stimulator of bone formation and may also function independently of IGFs. IGFBP-4 inhibits osteoblast function by sequestering IGF and preventing it from binding to its receptor. This review focuses on the specific IGF-dependent and IGF-independent roles of the IGFBPs in bone formation, as well as their potential mechanisms of action. In addition, discussion of the regulation of the IGFBPs by post-translational modification (i.e., proteolysis) has been included. Studies on the regulation of production and actions of IGFBPs suggest that the IGFBP system in bone is pleiotropic and capable of serving multiple effector inputs from systemic and local sources.

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Acknowledgements

This work was supported by funds from the National Institutes of Health (AR31062 and AR48139) and the Department of Veterans Affairs. We would like to thank Sean Belcher for his help in the preparation of this paper.

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Authors and Affiliations

  1. Musculoskeletal Disease Center, Jerry L. Pettis VA Medical Center, 11201 Benton Street, Loma Linda, CA 92357, USA

    Kristen E. Govoni, David J. Baylink & Subburaman Mohan

  2. Department of Medicine, Loma Linda University, Loma Linda, California, USA

    Kristen E. Govoni

  3. Department of Biochemistry, Loma Linda University, Loma Linda, California, USA

    David J. Baylink

  4. Departments of Medicine, Biochemistry and Physiology, Loma Linda University, Loma Linda, California, USA

    Subburaman Mohan

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  1. Kristen E. Govoni
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  2. David J. Baylink
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  3. Subburaman Mohan
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Correspondence to Subburaman Mohan.

Additional information

This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany

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Govoni, K.E., Baylink, D.J. & Mohan, S. The multi-functional role of insulin-like growth factor binding proteins in bone. Pediatr Nephrol 20, 261–268 (2005). https://doi.org/10.1007/s00467-004-1658-y

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  • DOI: https://doi.org/10.1007/s00467-004-1658-y

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