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Function of matrix IGF-1 in coupling bone resorption and formation

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Abstract

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

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Acknowledgments

This work was supported in part by the grants from the National Institute of Health, including T32DK007751 (JLC) and AR063943 and DK057501 (XC).

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The authors declare that they have no conflicts of interests.

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  1. Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Ross Building, Room 229, 720 Rutland Ave, Baltimore, MD, 21205, USA

    Janet L. Crane & Xu Cao

  2. Department of Pediatrics, Johns Hopkins University School of Medicine, Rubenstein Building, Room 3120, 200 N Wolfe St, Baltimore, MD 21287, USA

    Janet L. Crane

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  1. Janet L. Crane
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Crane, J.L., Cao, X. Function of matrix IGF-1 in coupling bone resorption and formation. J Mol Med 92, 107–115 (2014). https://doi.org/10.1007/s00109-013-1084-3

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  • DOI: https://doi.org/10.1007/s00109-013-1084-3

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