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

The influence of growth hormone (GH), insulin-like growth factor I (IG F-I), parathyroid hormone(1-34) (PTH(1-34)), 1,25-dihydroxycholecalcif erol (1,25(OH)2D3) and 17beta-oestradiol on proliferation and on produ ction of cytokines, such as interleukin-1beta (IL-1beta), IL-6, IL-8 a nd transforming growth factor-beta (TGF-beta), was studied in chondroc ytes 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 ch ondrocytes 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 ce lls in a dose-dependent manner. 17beta-oestradiol was stimulatory in S aOS-2 cells, but gave a biphasic pattern in chondrocytes; it was stimu latory at low concentrations (0.1 nmol/l) and inhibitory at supraphysi ological 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 cho ndrocytes, 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-oe stradiol, while PTH(1-34) had no effects. IL-8 was not influenced by G H 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 supraphysiolog ical doses. No detectable amounts of TGF-beta were found either in cho ndrocytes 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 fo rm that needs to be activated. These results show that hormones involv ed in growth, sexual maturation and calcium metabolism possess in vitr o stimulatory or inhibitory effects on cell proliferation. Furthermore , these hormones may regulate certain cytokines that are thought to in fluence some chondrocyte and osteoblast-like cell functions, but the r oles of these in bone growth need to be further elucidated.