Effects of interleukin-6 on cellular function in UMR-106-01 osteoblastlike cells.
High levels of interleukin-6 (IL-6) have been detected in synovial fluid from patients with inflammatory arthropathies associated with local bone resorption, suggesting a role for IL-6 as a local regulator of bone resorption and remodeling. In the present study we examined the effects of IL-6 on [3H]thymidine ([3H]TdR) incorporation, collagen synthesis, and alkaline phosphatase activity in UMR-106-01 rat osteoblastic osteosarcoma cells. IL-6 stimulated a dose-dependent increase in [3H]TdR incorporation that was maximal at 1000 U/ml (-147% of basal, p less than 0.005) in osteoblastlike cells that were in a logarithmic phase of growth. The increase in [3H]TdR incorporation was maximal between 12 and 24 h and was neutralized by pretreatment with the polyclonal rabbit antibody to IL-6. IL-6 also increased cell number and the secretion of prostaglandin E2 in UMR-106-01 cells in logarithmic growth phase. The stimulation of [3H]TdR incorporation and release of PGE2 into the culture medium by IL-6 was inhibited by indomethacin. A 24 h exposure of the osteoblastlike cells to 1000 U/ml of IL-6 reduced [3H]proline incorporation into collagenase-digestible (CDP) protein to 73% of control values (p less than 0.01). Noncollagen protein (NCP) synthesis was inhibited to 80% of control values (p less than 0.01) by 1000 U/ml of IL-6. The inhibitory effect was relatively greater on CDP than on NCP and consequently resulted in a decrease in the percentage of collagen synthesis. Alkaline phosphatase activity was not altered in these cells after a 24 h exposure to 1-1000 U/ml of IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)
Fang
M A
MA
Rheumatology Section, Wadsworth VA Medical Center, Los Angeles, CA.
Hahn
T J
TJ
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D011506:Proteins; D014316:Tritium; D003094:Collagen; D000469:Alkaline Phosphatase; D015232:Dinoprostone; D013936:Thymidine; D007213:Indomethacin