IN-VITRO EFFECTS OF GROWTH-HORMONE AND OTHER HORMONES ON CHONDROCYTES AND OSTEOBLAST-LIKE CELLS

The influence of growth hormone (GH), insulin-like growth factor I (IGF-I), parathyroid hormone(1-34) (PTH(1-34)), 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 17beta-oestradiol on proliferation and on production of cytokines, such as interleukin-1beta (IL-1beta), IL-6, IL-8 and transforming growth factor-beta (TGF-beta), was studied in chondrocytes obtained from the growing cartilage of the iliac crest and in the osteoblast-like cell clone SaOS-2. GH and IGF-I were mitogenic for chondrocytes and SaOS-2 cells, as indicated by the dose-related increase in uptake of [H-3]thymidine. PTH(1-34) was also mitogenic, while 1,25(OH)2D3 inhibited the proliferation of both chondrocytes and SaOS-2 cells in a dose-dependent manner. 17beta-oestradiol was stimulatory in SaOS-2 cells, but gave a biphasic pattern in chondrocytes; it was stimulatory at low concentrations (0.1 nmol/l) and inhibitory at supraphysiological doses (10 nmol/l). Using the cDNA polymerase chain reaction, specific mRNAs for IL-1beta, IL-6, IL-8 and TGF-beta were found in chondrocytes, while SaOS-2 cells had a positive signal only for TGF-beta. Specific enzyme immunoassays revealed detectable levels of IL-1beta, IL-6 and IL-8 only in chondrocytes. IL-6 was increased by GH and IGF-1, and lowered by 1,25(OH)2D3 and supraphysiological doses of 17beta-oestradiol, while PTH(1-34) had no effects. IL-8 was not influenced by GH or IGF-I, was slightly but not significantly increased by PTH(1-34) and was reduced by 1,25(OH)2D3 and 17beta-oestradiol at supraphysiological doses. No detectable amounts of TGF-beta were found either in chondrocytes or in SaOS-2 cells using an enzyme immunoassay specific for TGF-beta2; it is likely that the cells produce TGF-beta in a latent form that needs to be activated. These results show that hormones involved in growth, sexual maturation and calcium metabolism possess in vitro stimulatory or inhibitory effects on cell proliferation. Furthermore, these hormones may regulate certain cytokines that are thought to influence some chondrocyte and osteoblast-like cell functions, but the roles of these in bone growth need to be further elucidated.