TY - JOUR
T1 - Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells
AU - Hofbauer, L. C.
AU - Lacey, D. L.
AU - Dunstan, C. R.
AU - Spelsberg, T. C.
AU - Riggs, B. L.
AU - Khosla, S.
N1 - Funding Information:
The authors acknowledge the technical assistance of M. J. Schroeder, B. Ngo, and R. A. Soderberg. This work was supported by Grant AG-04875 from the National Institutes of Health. Dr. Hofbauer is a recipient of a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (Ho 1875/1-1).
PY - 1999/9
Y1 - 1999/9
N2 - Recent studies have identified osteoprotegerin ligand (OPG-L) as the essential factor required for osteoclastogenesis, and that the effects are prevented by its soluble receptor, osteoprotegerin (OPG). However, there are limited data at present on the regulation of OPG-L expression in human osteoblastic cells by other cytokines. Because interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 all increase osteoclastogenesis, we assessed whether OPG-L mRNA steady-state levels were regulated by these cytokines in human osteoblastic cells. By northern analysis, IL-1β (5 nmol/L) and TNF-α (9 nmol/L) increased OPG-L mRNA steady-state levels by up to two- to three-fold in normal marrow stromal cells (MS), an immortalized marrow stromal cell line (hMS), and the osteosarcoma cell line, MG-63, whereas IL-6 (2 nmol/L, with or without its soluble receptor) had no effect on OPG-L mRNA levels in any of these cells. IL-1β and TNF-α increased OPG-L mRNA steady-state levels in the normal MS cells and the hMS cell line in a time- and dose-dependent fashion by up to 4.1-fold and up to 2.6-fold, respectively. Our data are thus consistent with the hypothesis that the proinflammatory and bone-resorbing cytokines, IL-1β and TNF-α, but not IL-6, may stimulate osteoclastogenesis by inducing the expression of OPG-L. Copyright (C) 1999 Elsevier Science Inc.
AB - Recent studies have identified osteoprotegerin ligand (OPG-L) as the essential factor required for osteoclastogenesis, and that the effects are prevented by its soluble receptor, osteoprotegerin (OPG). However, there are limited data at present on the regulation of OPG-L expression in human osteoblastic cells by other cytokines. Because interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 all increase osteoclastogenesis, we assessed whether OPG-L mRNA steady-state levels were regulated by these cytokines in human osteoblastic cells. By northern analysis, IL-1β (5 nmol/L) and TNF-α (9 nmol/L) increased OPG-L mRNA steady-state levels by up to two- to three-fold in normal marrow stromal cells (MS), an immortalized marrow stromal cell line (hMS), and the osteosarcoma cell line, MG-63, whereas IL-6 (2 nmol/L, with or without its soluble receptor) had no effect on OPG-L mRNA levels in any of these cells. IL-1β and TNF-α increased OPG-L mRNA steady-state levels in the normal MS cells and the hMS cell line in a time- and dose-dependent fashion by up to 4.1-fold and up to 2.6-fold, respectively. Our data are thus consistent with the hypothesis that the proinflammatory and bone-resorbing cytokines, IL-1β and TNF-α, but not IL-6, may stimulate osteoclastogenesis by inducing the expression of OPG-L. Copyright (C) 1999 Elsevier Science Inc.
KW - IL-6
KW - Interleukin (IL)-1β
KW - Osteoblast
KW - Osteoprotegerin
KW - Osteoprotegerin ligand
KW - Tumor necrosis factor-α (TNF-α)
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U2 - 10.1016/S8756-3282(99)00162-3
DO - 10.1016/S8756-3282(99)00162-3
M3 - Article
C2 - 10495128
AN - SCOPUS:0032588998
SN - 8756-3282
VL - 25
SP - 255
EP - 259
JO - Bone
JF - Bone
IS - 3
ER -