INSULIN-LIKE GROWTH-FACTOR (IGF)-I, (IGF)-II, IGF-BINDING-PROTEINS (IGFBP)-3, (IGFBP)-4, AND (IGFBP)-5 LEVELS IN THE CONDITIONED MEDIA OF NORMAL HUMAN BONE-CELLS ARE SKELETAL SITE-DEPENDENT

The skeleton in its function of affording strength and support to the body is subject to differential mechanical loading which has been impl icated to mediate some of its effects on bone formation via the insuli n-like growth factors (IGFs), which are important regulators of bone m etabolism, We, therefore, sought to conduct the present study with the hypothesis that the skeletal site-dependent differences in mechanical loading and other variables including stage of osteoblast differentia tion would be associated with site-specific differences in the product ion of the IGF system components, To test this hypothesis, conditioned media (CM) from normal human bone cells (control and IGF-II-treated 4 8-h cultures) from five different skeletal sites were obtained and ass ayed for IGF-I, IGF-LI (following separation of IGF binding proteins [ IGFBPs]), IGFBP-3, IGFBP-4, and IGFBP-5 protein levels employing speci fic radioimmunoassays for each protein, IGF-I levels were lower than a ny other IGF system component but were significantly different between the various sites tested, IGF-II levels were greatest in the CM from mandibular cells, followed by calvarial and rib cells, and least in th e marrow stromal cells, IGFBP-3 levels were highest in the CM of verte bral cells and lowest in the CM of rib and mandibular cells, The relat ive abundance of IGFBP-4 in decreasing order,vas observed in mandibula r, calvarial, vertebral, rib, and stromal cells' CM, IGFBP-5 was produ ced maximally by the calvarial cells, followed by the mandibular, vert ebral, stromal, and rib cells, IGFBP-4 appeared to be the IGF system c omponent most abundantly produced by all the cell types from the skele tal sites tested, On a molar basis, the IGFBPs in general were estimat ed to be produced at a higher magnitude than the IGFs, These findings indicate that there are skeletal site-dependent differences in the pro duction of IGF system components and suggest that the regulation of bo ne metabolism may vary at the various skeletal sites.