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Alendronate/Interleukin‐1β Cotreatment Increases Interleukin‐6 in Bone and UMR‐106 Cells: Dose Dependence and Relationship to the Antiresorptive Effect of Alendronate
Author(s) -
Sanders Jennifer L.,
Tarjan Gabor,
Foster Shirley A.,
Stern Paula H.
Publication year - 1998
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 - 10.1359/jbmr.1998.13.5.786
Subject(s) - bone resorption , medicine , endocrinology , osteoblast , bisphosphonate , interleukin , resorption , alendronic acid , bone cell , cytokine , chemistry , osteoporosis , in vitro , biochemistry
Abstract Aminobisphosphonates inhibit bone resorption but have been shown to elicit acute‐phase‐like elevations in interleukin‐6 (IL‐6) in bone in vitro. The current studies were carried out to determine the relationship between the antiresorptive effects of the aminobisphosphonate alendronate and its effects on IL‐6. Resorption was elicited in cultured 19‐day fetal rat limb bones by 72 h treatment with interleukin‐1β (IL‐1β). Bone mass was quantitated at the end of the culture period to assess resorption. IL‐6 was determined by bioassay (7TD1 cell proliferation). IL‐1β (18 and 180 pM) stimulated bone resorption and increased IL‐6. Alendronate (70 μM) inhibited the IL‐1β–stimulated resorption. Alendronate alone did not affect IL‐6 production by the bones. The IL‐6 production from bones stimulated with 18 pM IL‐1β was not significantly affected by alendronate, but the IL‐6 production from bones stimulated with 180 pM IL‐1β plus alendronate (21 and 70 μM) was higher than with IL‐1β alone. Indomethacin (1 mM) inhibited the IL‐6 increase elicited by 180 pM IL‐1β and the enhanced IL‐6 production elicited by cotreatment with IL‐1β and alendronate. Since bone cultures contain multiple cell types, further experiments were carried out to determine whether alendronate could increase IL‐1β–stimulated IL‐6 production in an osteoblast cell line, UMR‐106. Alendronate alone did not affect IL6 in UMR‐106 cells. Alendronate (70 μM) in combination with IL‐1β (180, 1.8, or 8 nM), or 7 μM alendronate, in combination with 8 nM IL‐1β, significantly increased IL‐6 in 48 h cell cultures. The results from the bone organ cultures show that alendronate can enhance IL‐6 production elicited by higher concentrations of the cytokine IL‐1β in bone, but that this effect on IL‐6 does not prevent the inhibitory actions of alendronate on bone resorption. The results with the UMR106 cells indicate that one cellular site at which this enhancement of IL‐6 production can occur is the osteoblast.