Mitogenic activity of hydroxyapatite: requirement for somatomedin C.
Synovial hyperplasia is a feature of the chronic synovitis associated with basic calcium phosphate crystals [hydroxyapatite (HA), octacalcium phosphate, tricalcium phosphate] and calcium pyrophosphate. Each of these crystals stimulated mitosis of cultured human skin fibroblasts or canine synovial fibroblasts in a concentration-dependent fashion. We examined the effect of pure somatomedin C (Sm-C) on HA crystal induced mitogenesis. Confluent cultures of human fibroblasts were rendered quiescent by incubation in the presence of 1% platelet-poor-Sm-C free plasma (PPSCFP) for 24 hours. HA crystals stimulated thymidine incorporation 2.3-fold over control value. Addition of Sm-C significantly augmented the effect of HA crystals (P less than 0.01). Nearly identical effects were observed in the presence of 100 micrograms/ml HA crystals or 15 ng/ml PDGF. Monoclonal antibodies against Sm-C had little effect on the basal 3H thymidine uptake by control cells incubated in 1% PPSCFP but blocked over 50% of the HA crystal or PDGF-induced 3H thymidine incorporation both in the presence or absence of Sm-C. The incomplete blocking suggested either the presence of other "progression" factors, such as insulin-like growth factor II in the conditioned media or the possibility that HA or PDGF in high enough dosage enabled cells to escape their dependence on Sm-C for DNA synthesis.
D002478:Cells, Cultured; D003460:Crystallization; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D017886:Durapatite; D005347:Fibroblasts; D006801:Humans; D006882:Hydroxyapatites / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D003470:Culture Media; D006882:Hydroxyapatites; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017886:Durapatite; D013936:Thymidine