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Tumor necrosis factors α and β can stimulate bone resorption in cultured mouse calvariae by a Prostaglandin‐independent mechanism
Author(s) -
Lerner Ulf H.,
Ohlin Acke
Publication year - 1993
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.5650080205
Subject(s) - tumor necrosis factor alpha , prostaglandin e2 , endocrinology , bone resorption , medicine , prostaglandin e , chemistry , cyclooxygenase , alpha (finance) , flurbiprofen , prostaglandin , beta (programming language) , pharmacology , biochemistry , enzyme , construct validity , nursing , computer science , programming language , patient satisfaction
Human recombinant tumor necrosis factors α and β (TNF‐α and TNF‐β), at and above 1 ng/ml (≅ 70 pM), caused a dose‐ and time‐dependent enhancement of 45 Ca release from neonatal mouse calvarial bones in vitro. In addition, TNF‐α and TNF‐β (3–100 ng/ml) caused a dose‐dependent stimulation of prostaglandin E 2 (PGE 2 ) formation in the calvarial bones. TNF‐α also enhanced the biosynthesis of PGI 2 , as assessed by analysis of the stable breakdown product 6‐keto‐PGF 1α . The stimulatory actions of TNF‐α and TNF‐β on PGE 2 formation was maximal at 12 h. Indomethacin, flurbiprofen, and meclofenamic acid, three structurally unrelated nonsteroidal antiinflammatory drugs, abolished PGE 2 biosynthesis induced by TNF‐α and TNF‐β (100 ng/ml). The 45 Ca release stimulated by TNF‐α and TNF‐β (100 ng/ml), however, was only slightly reduced by indomethacin, flurbiprofen, and meclofenamic acid. The partial inhibitory effect of indomethacin on 45 Ca release was seen over a wide range of TNF‐α concentrations, without affecting the concentration producing half‐maximal stimulatory response. TNF‐α and TNF‐β (100 ng/ml) stimulated bone matrix breakdown, as assessed by analysis of the release of 3 H from bone prelabeled with [ 3 H]proline. Also, the stimulatory effect of TNF‐α and TNF‐β on bone matrix degradation was partially reduced by indomethacin. Hydrocortisone (1 μM) and dexamethasone (0.1 μM) abolished TNF‐α‐ and TNF‐β‐induced production of PGE 2 . In contrast to the cyclooxygenase inhibitors, the corticosteroids did not affect the stimulatory action by the cytokines on 45 Ca release. These observations suggest that TNF‐α and TNF‐β can stimulate bone resorption in vitro by prostaglandin‐independent mechanisms.