Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone.
Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.
Scheven
B A
BA
Rowett Research Institute, Bucksburn, Aberdeen, UK.
Hamilton
N J
NJ
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002455:Cell Division; D003470:Culture Media / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005333:Fetus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013006:Growth Hormone / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000911:Antibodies, Monoclonal; D003470:Culture Media; D006133:Growth Substances; D011994:Recombinant Proteins; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004247:DNA; D013936:Thymidine