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Effects of interleukin‐6 on cellular function in UMR‐106–01 osteoblastlike cells
Author(s) -
Fang Meika A.,
Hahn Theodore J.
Publication year - 1991
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650060206
Subject(s) - endocrinology , medicine , bone resorption , alkaline phosphatase , collagenase , chemistry , prostaglandin e2 , calvaria , interleukin , resorption , stimulation , cytokine , biology , in vitro , biochemistry , enzyme
Abstract 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.