Jb. Rosenquist et al., CYTOKINE-INDUCED INHIBITION OF BONE-MATRIX PROTEINS IS NOT MEDIATED BY PROSTAGLANDINS, Inflammation research, 45(9), 1996, pp. 457-463
Interleukin-1 (IL-1) and tumor necrosis factor (TNF), two pleiotropic
cytokines produced in inflammatory processes, inhibit bone matrix bios
ynthesis and stimulate prostanoid formation in osteoblasts. In the pre
sent study, the importance of prostaglandin formation in IL-1 and TNF-
induced inhibition of osteocalcin and type I collagen formation has be
en 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) stimu
lated prostaglandin E(2) (PGE(2)) formation and inhibited 1,25(0H)(2)-
vitamin D3-induced osteocalcin biosynthesis as well as basal productio
n of type I collagen. Addition of PGE(2) or increasing the endogenous
formation of PGE(2) by treating the cells with arachidonic acid, brady
kinin, Lys-bradykinin or des-Arg(9)-bradykinin, did not affect osteoca
lcin and type I collagen formation in unstimulated or 1,25(OH)(2)-vita
min D3-stimulated osteoblasts. Four non-steroidal antiinflammatory dru
gs, indomethacin, flurbiprofen, naproxen and meclofenamic acid, inhibi
ted basal, IL-1 beta-and TNF-alpha-stimulated PGE(2) formation in the
MG-63 cells without affecting IL-1 beta- or TNF-alpha-induced inhibiti
on of osteocalcin and type I collagen formation. In isolated, non-tran
sformed, human osteoblast-like cells, IL-1 beta and TNF-beta stimulate
d PGE(2) 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 th
e effects of IL-1 beta and TNF-alpha on prostaglandin formation withou
t affecting the inhibitory effects of the cytokines on osteocalcin bio
synthesis. These data show that IL-1 and TNF inhibit osteocalcin and t
ype I collagen formation in osteoblasts independently of prostaglandin
biosynthesis and that non-steroidal antiinflammatory drugs do not aff
ect the effects of IL-1 and TNF on bone matrix biosynthesis.