Insulin-Like Growth Factor I Has Independent Effects on Bone Matrix Formation and Cell Replication*

Abstract

The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of [2,3-3H]proline and [methyl-3H]thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on [3H]proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on [3H]thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis.

Interaction Between Clinical and Laboratorys Indicators and Genetic Polymorphysms of the Calcaneal Bone Mineral Density in Children Starting Puberty. Is this a Time for Intervention?

“…While a number of studies have resonated such results in the elderly, studies in children are more scarse and often not focused on a trait that is believed to be important mainly in elderly 4,6]. This study shows that some of the genes involved in bone metabolism also maintained their effect in the regression model that involved a number of behavioural patterns and other indicators, supporting some previous claims that genetic effects on bone could be strongly expressed in younger age [28][29][30][31][32][33][34][35][36][37][38][39][40][41].…”

“…These results also resonate an important message in the sphere of public health, that physical activity and calcium intake about 850 mg /per day [40,41] are important even in the pubertal life and that commonly heard proposals that impaired BMD is a problem of elderly might not be completely true. Focus of the preventive activities related to osteoporosis should be more systematic and transferred to even younger age, when improvements might be more feasible and easier to achieve [29][30][31][32][33][34][35].…”

Stimulatory Effect of Wasabi Leafstalk Extract (Wasabia japonica MATSUM.) on Bone Calcification: Interaction with Bone Anabolic Factors in Mouse Calvaria Tissue in Vitro

“…Moreover, it is possible that the extract may enhance transcription activity which is mediated through 17␤-estradiol or genistein action in the nucleus of these cells. Insulin or IGF-I has been shown to stimulate bone formation in osteoblastic cells (Levy et al , 1986;Kream et al , 1985;Hock et al , 1988;Schmid et al , 1989;Canalis et al , 1993). The receptors of insulin or IGF-I are located on the plasma membranes of these cells (Ituarte et al , 1989;Centrella et al , 1990), and the actions of these factors are mediated through signal transduction in osteoblastic cells (Saltiel et al , 1987;Canalis et al , 1993).…”

Review of the History of Materials Used With Experience with Bone Cement Cranioplasty

“…Use of recombinant factors such as transforming growth factor b, insulin-like growth factor-I, and BMP-2 and tissue engineering in augmenting calvarial closure in animal and human models are being studied. 16,28,36 Stem Cell-Based Therapies Recent advances in laboratory research have shifted the focus from osteoconduction to a more osteoinductive framework, whereby undifferentiated mesenchymal cells can be transformed into osteoprogenitor cells in situ. Stem cell-based therapies hold enormous promise in this regard, demonstrating successful repair of critical-sized cranial defects by using human induced pluripotent stem cells (iPSCs), bone marrow derived stem cells (BMSCs), and adipose-derived stem cells (ASCs) in mouse models.…”