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 [ 3 H]thymidine ([ 3 H]TdR) incorporation, collagen synthesis, and alkaline phosphatase activity in UMR‐106–01 rat osteoblastic osteosarcoma cells. IL‐6 stimulated a dose‐dependent increase in [ 3 H]TdR incorporation that was maximal at 1000 U/ml (+147% of basal, p < 0.005) in osteoblastlike cells that were in a logarithmic phase of growth. The increase in [ 3 H]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 E 2 in UMR‐106–01 cells in logarithmic growth phase. The stimulation of [ 3 H]TdR incorporation and release of PGE 2 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 [ 3 H]proline incorporation into collagenase‐digestible (CDP) protein to 73% of control values (p < 0.01). Noncollagen protein (NCP) synthesis was inhibited to 80% of control values (p < 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. These results indicate that IL‐6 has a direct effect on osteoblastlike cells, stimulating DNA synthesis via a prostaglandin‐dependent mechanism and suppressing collagen and noncollagen protein synthesis.