The effect of interleukin-6 and soluble interleukin-6 receptor protein on the bone resorptive activity of human osteoclasts generated in vitro.
The role of interleukin-6 (IL-6) in the regulation of bone resorption is controversial and has not been studied using human tissue in vitro. This study exploits a recently described in vitro model, whereby osteoclasts, defined as cells that resorb bone, can be generated from human bone marrow, and investigated the effect of IL-6 and its soluble receptor on bone resorption, in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2 vitamin D3]. Human bone marrow was cultured to form a confluent stroma, sedimented onto devitalized bone slices, and recharged with non-adherent bone marrow cells. 1,25(OH)2 vitamin D3 increased bone resorption, whereas IL-6 failed to induce a similar stimulatory effect. Both IL-6 at 100 ng/ml and soluble IL-6 receptor protein in the absence of exogenous IL-6 inhibited the stimulatory effect of 1,25(OH)2 vitamin D3. Bone resorption was never observed when non-adherent haemopoietic cells were cultured in the absence of stroma but in the presence of IL-6, which indicates that IL-6 cannot replace the stromal factor(s) required for the formation of cells capable of resorbing bone. These results suggest that IL-6 at high concentrations is not a critical cytokine in stimulating osteoclastic bone resorption.
Flanagan
A M
AM
Department of Histopathology, Imperial College of Science, St Mary's Hospital, London, UK.
Stow
M D
MD
Williams
R
R
D000328:Adult; D001854:Bone Marrow Cells; D001862:Bone Resorption / Q000473:pathology*; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects*; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D012995:Solubility; D017154:Stromal Cells / Q000502:physiology
D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D002117:Calcitriol