Cytokine-induced inhibition of bone matrix proteins is not mediated by prostaglandins.
Interleukin-1 (IL-1) and tumor necrosis factor (TNF), two pleiotropic cytokines produced in inflammatory processes, inhibit bone matrix biosynthesis and stimulate prostanoid formation in osteoblasts. In the present study, the importance of prostaglandin formation in IL-1 and TNF-induced inhibition of osteocalcin and type I collagen formation has been examined. In the human osteoblastic cell line MG-63, IL-1 alpha (10-1000 pg/ml), IL-1 beta (3-300 pg/ml) and TNF-alpha (1-30 ng/ml) stimulated prostaglandin E2 (PGE2) formation and inhibited 1,25(OH)2-vitamin D3-induced osteocalcin biosynthesis as well as basal production of type I collagen. Addition of PGE2 or increasing the endogenous formation of PGE2 by treating the cells with arachidonic acid, bradykinin, Lys-bradykinin or des-Arg9-bradykinin, did not affect osteocalcin and type I collagen formation in unstimulated or 1,25(OH)2-vitamin D3-stimulated osteoblasts. Four non-steroidal antiinflammatory drugs, indomethacin, flurbiprofen, naproxen and meclofenamic acid, inhibited basal, IL-1 beta- and TNF-alpha-stimulated PGE2 formation in the MG-63 cells without affecting IL-1 beta- or TNF-alpha-induced inhibition of osteocalcin and type I collagen formation. In isolated, non-transformed, human osteoblast-like cells, IL-1 beta and TNF-alpha stimulated PGE2 formation and concomitantly inhibited 1,25(OH)2-vitamin D3-stimulated osteocalcin biosynthesis, without affecting type I collagen formation. In these cells, indomethacin and flurbiprofen abolished the effects of IL-1 beta and TNF-alpha on prostaglandin formation without affecting the inhibitory effects of the cytokines on osteocalcin biosynthesis. These data show that IL-1 and TNF inhibit osteocalcin and type I collagen formation in osteoblasts independently of prostaglandin biosynthesis and that non-steroidal antiinflammatory drugs do not affect the effects of IL-1 and TNF on bone matrix biosynthesis.
Rosenquist
J B
JB
Department of Oral and Maxillofacial Surgery, Lund University, Malmö General Hospital, Sweden.
Ohlin
A
A
Lerner
U H
UH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001857:Bone Matrix / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015675:Osteocalcin / Q000096:biosynthesis*; D011453:Prostaglandins / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D003094:Collagen; D002117:Calcitriol; D015232:Dinoprostone