Insulin-Like Growth Factor-I Is Essential for Embryonic Bone Development

Hospital for Special Surgery, New York, New York, United States
Endocrinology (Impact Factor: 4.5). 11/2006; 147(10):4753-61. DOI: 10.1210/en.2006-0196
Source: PubMed


Although IGF-I has been identified as an important growth factor for the skeleton, the role of IGF-I on embryonic bone development remains unknown. Here we show that, in IGF-I-deficient (IGF-I(-/-)) mice, skeletal malformations, including short-limbed dwarfism, were evident at days post coitus (dpc) 14.5 to 18.5, accompanied by delays of mineralization in the spinal column, sternum, and fore paws. Reduced chondrocyte proliferation and increased chondrocyte apoptosis were identified in both the spinal ossification center and the growth plate of long bones. Abnormal chondrocyte differentiation and delayed initiation of mineralization was characterized by small size and fewer numbers of type X collagen expressing hypertrophic chondrocytes and lower osteocalcin expression. The Indian hedgehog-PTHrP feedback loop was altered; expression of Indian hedgehog was reduced in IGF-I(-/-) mice in long bones and in the spine, whereas expression of PTHrP was increased. Our results indicate that IGF-I plays an important role in skeletal development by promoting chondrocyte proliferation and maturation while inhibiting apoptosis to form bones of appropriate size and strength.

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Available from: Hashem Elalieh, Apr 15, 2014
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    • "Unlike skeletal muscle, in which IGF-1 does not appear to be necessary for the mechanicallyinduced increase in mTORC1 signaling and skeletal muscle mass, bone cell mechanotransduction requires IGF-1 signaling for the anabolic effects of loading. For instance, IGF-1 is known to play an essential role in embryonic bone development [183] [184] and early studies also suggested a potential role for IGF-1 in the regulation of bone mass in response to changes in mechanical loading. Specifically, studies conducted in mechanically stimulated osteocytes in vitro, and in mechanically stimulated rat vertebrae and tibia in vivo, revealed increased expression of IGF-1 mRNA expression after a bout of increased loading [185] [186] [187]. "
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    ABSTRACT: The development and maintenance of skeletal muscle and bone mass is critical for movement, health and issues associated with the quality of life. Skeletal muscle and bone mass are regulated by a variety of factors that include changes in mechanical loading. Moreover, bone mass is, in large part, regulated by muscle-derived mechanical forces and thus by changes in muscle mass/strength. A thorough understanding of the cellular mechanism(s) responsible for mechanotransduction in bone and skeletal muscle is essential for the development of effective exercise and pharmaceutical strategies aimed at increasing, and/or preventing the loss of, mass in these tissues. Thus, in this review we will attempt to summarize the current evidence for the major molecular mechanisms involved in mechanotransduction in skeletal muscle and bone. By examining the differences and similarities in mechanotransduction between these two tissues, it is hoped that this review will stimulate new insights and ideas for future research and promote collaboration between bone and muscle biologists.
    Bone 04/2015; in press. DOI:10.1016/j.bone.2015.04.014 · 3.97 Impact Factor
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    • "Two growth factors that seem particularly important for differentiation towards IVD-like cells are IGF-1 and TGF-β1. IGF-1 and its receptor have been shown to be expressed in the IVD [57,58], and IGF-1 has been shown to have an effect on early dorso-anterior (notochord) development [59] and to promote chondrocyte differentiation and embryonic bone development [60]. Members of the TGF-β family and receptors are expressed in the IVD [57,58], and TGF-β1 was reported to be able to induce rat MSCs to differentiation to a phenotype consistent with NP on alginate hydrogels [19]. "
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    Stem Cell Research & Therapy 10/2013; 4(5):120. DOI:10.1186/scrt331 · 3.37 Impact Factor
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    • "As expected, BMP-2 expression particularly in hypertrophic chondrocytes of the growth plate was increased in the laser acupuncture-treated group compared with the control group (Figure 4(a), arrow denotes brown staining indicative of BMP-2 expression). IGF-1 is an important factor to augment longitudinalbone growth by stimulating growth plate chondrocyte proliferation [25]. IGF-1 immunostaining was relatively higher in the proliferative zone than the hypertrophic zone. "
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