Anabolic effects of IGF-1 signaling on the skeleton
- Endocrine Research Unit, Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco, CA, USA
This review focuses on the anabolic effects of IGF-1 signaling on the skeleton, emphasizing the requirement for IGF-1 signaling in normal bone formation and remodeling. We first discuss the genomic context, splicing variants, and species conservation of the IGF-1 locus. The modulation of IGF-1 action by growth hormone (GH) is then reviewed while also discussing the current model which takes into account the GH-independent actions of IGF-1. Next, the skeletal phenotypes of IGF-1-deficient animals are described in both embryonic and postnatal stages of development, which include severe dwarfism and an undermineralized skeleton. We then highlight two mechanisms by which IGF-1 exerts its anabolic action on the skeleton. Firstly, the role of IGF-1 signaling in the modulation of anabolic effects of parathyroid hormone (PTH) on bone will be discussed, presenting in vitro and in vivo studies that establish this concept and the proposed underlying molecular mechanisms involving Indian hedgehog (Ihh) and the ephrins. Secondly, the crosstalk of IGF-1 signaling with mechanosensing pathways will be discussed, beginning with the observation that animals subjected to skeletal unloading by hindlimb elevation are unable to mitigate cessation of bone growth despite infusion with IGF-1 and the failure of IGF-1 to activate its receptor in bone marrow stromal cell cultures from unloaded bone. Disrupted crosstalk between IGF-1 signaling and the integrin mechanotransduction pathways is discussed as one of the potential mechanisms for this IGF-1 resistance. Next, emerging paradigms on bone-muscle crosstalk are examined, focusing on the potential role of IGF-1 signaling in modulating such interactions. Finally, we present a future outlook on IGF research.
Keywords: IGF-1, osteogenesis, skeletal unloading, mechanotransduction, PTH, integrins, muscle-bone interactions
Citation: Tahimic CGT, Wang Y and Bikle DD (2013) Anabolic effects of IGF-1 signaling on the skeleton. Front. Endocrin. 4:6. doi: 10.3389/fendo.2013.00006
Received: 15 December 2012; Paper pending published: 31 December 2012;
Accepted: 16 January 2013; Published online: 04 February 2013.
, University of Barcelona, Spain
, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
Copyright: © 2013 Tahimic, Wang and Bikle. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Daniel D. Bikle, Endocrine Research Unit, Veterans Affairs Medical Center (111N), Department of Medicine, University of California, 4150 Clement Street, San Francisco, CA 94121, USA. e-mail: email@example.com