title: Osteocyte-derived insulin-like growth factor I is not essential for the bone repletion response in mice.
abstract: The present study sought to evaluate the functional role of osteocyte-derived IGF-I in the bone repletion process by determining whether deficient expression of Igf1 in osteocytes would impair the bone repletion response to one week of dietary calcium repletion after two weeks of dietary calcium deprivation. As expected, the two-week dietary calcium depletion led to hypocalcemia, secondary hyperparathyroidism, and increases in bone resorption and bone loss in both Igf1 osteocyte conditional knockout (cKO) mutants and WT control mice. Thus, conditional disruption of Igf1 in osteocytes did not impair the calcium depletion-induced bone resorption. After one week of calcium repletion, both cKO mutants and WT littermates showed an increase in endosteal bone formation attended by the reduction in osteoclast number, indicating that deficient Igf1 expression in osteocytes also did not have deleterious effects on the bone repletion response. The lack of an effect of deficient osteocyte-derived IGF-I expression on bone repletion is unexpected since previous studies show that these Igf1 osteocyte cKO mice exhibited impaired developmental growth and displayed complete resistance to bone anabolic effects of loading. These studies suggest that there is a dichotomy between the mechanisms necessary for anabolic responses to mechanical loading and the regulatory hormonal and anabolic skeletal repletion following low dietary calcium challenge. In conclusion, to our knowledge this study has demonstrated for the first time that osteocyte-derived IGF-I, which is essential for anabolic bone response to mechanical loading, is not a key regulatory factor for bone repletion after a low calcium challenge.
authors: Division of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, United States of America; Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, California, United States of America.
authors: Kin-Hing William
authors: KH
authors: Lau
authors: Division of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors: David J
authors: DJ
authors: Baylink
authors: Division of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors: Matilda H-C
authors: MH
authors: Sheng
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics*; D001862:Bone Resorption / Q000178:diet therapy / Q000235:genetics / Q000503:physiopathology; D002136:Calcium, Dietary / Q000008:administration & dosage; D006996:Hypocalcemia / Q000378:metabolism / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism; D010012:Osteogenesis
chemical_list: D002136:Calcium, Dietary; D007334:Insulin-Like Growth Factor I
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