Differential stimulation by PGE(2) and calcemic hormones of IL-6 in stromal/osteoblastic cells.
Formation of osteoclast-like cells in mouse bone marrow cultures induced by either 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), parathyroid hormone (PTH) or prostaglandin E(2) (PGE(2)), respectively, shows partial dependence on interleukin-6 receptor (IL-6R) activation. This suggests that locally produced IL-6 could be relevant for osteoclast formation. Therefore, we evaluated the effects of 1,25-(OH)(2)D(3), PTH, and PGE(2) on IL-6 production in stromal/osteoblastic cell lines. It appeared that these bone resorptive factors differed widely in their ability to modulate IL-6 mRNA expression and, consequently, protein synthesis in each of the cell lines studied. While 1,25-(OH)(2)D(3) was marginally effective only in ST2 cells, and PTH caused a 2- to 20-fold increase in IL-6 levels MC3T3-E1 and UMR-106 cells, PGE(2) enhanced IL-6 production in the ST2 and MC3T3-E1 cell line by two to three orders of magnitude, respectively, and also induced IL-6 in fibroblastic L929 cells. PGE(2)-stimulated IL-6 release from mesenchymal cells seems to be important for autocrine/paracrine control of osteoclast formation in health and disease.
Gruber
R
R
Department of Pathophysiology, University of Vienna Medical School, Vienna, A-1090, Austria.
Nothegger
G
G
Ho
G M
GM
Willheim
M
M
Peterlik
M
M
D016475:3T3 Cells; D000818:Animals; D001859:Bone Neoplasms; D002117:Calcitriol / Q000494:pharmacology*; D002417:Cattle; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D012516:Osteosarcoma; D019947:Receptors, Interleukin-6 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D019379:Teriparatide / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D019379:Teriparatide; D002117:Calcitriol; D015232:Dinoprostone