Mode of Action of Interleukin-6 on Mature Osteoclasts. Novel Interactions with Extracellular Ca2+ Sensing in the Regulation of Osteoclastic Bone Resorption

We describe a physiologically significant mechanism through which interleukin-6 (IL-6) and a rising ambient Ca2+ interact to regulate osteoclastic bone resorption. VOXEL-based confocal microscopy of nonpermeabilized osteoclasts incubated with anti-IL-6 receptor antibodies revealed intense, strictly...

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Bibliographic Details
Published in:The Journal of cell biology 1998-09, Vol.142 (5), p.1347-1356
Main Authors: Adebanjo, Olugbenga A., Moonga, Baljit S., Yamate, Tomoo, Sun, Li, Minkin, Cedric, Abe, Etsuko, Zaidi, Mone
Format: Article
Language:English
Subjects:
Animals
Antibodies
Bone resorption
Bone Resorption - metabolism
Bones
Calcium
Calcium - metabolism
Cells
Cellular biology
Cytokines
Fluorescent Antibody Technique
In Situ Hybridization, Fluorescence
Interleukin-11 - pharmacology
Interleukin-6 - metabolism
Interleukin-6 - pharmacology
Leukocytes
Membrane Proteins - analysis
Messenger RNA
Nickel - pharmacology
Osteoclasts
Osteoclasts - physiology
Rats
Receptors
Receptors, Interleukin-6 - analysis
RNA, Messenger - metabolism
Secretion
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Summary:We describe a physiologically significant mechanism through which interleukin-6 (IL-6) and a rising ambient Ca2+ interact to regulate osteoclastic bone resorption. VOXEL-based confocal microscopy of nonpermeabilized osteoclasts incubated with anti-IL-6 receptor antibodies revealed intense, strictly peripheral plasma membrane fluorescence. IL-6 receptor expression in single osteoclasts was confirmed by in situ reverse transcriptase PCR histochemistry. IL-6 (5 ng/l to 10 μg/l), but not IL-11 (10 and 100 μg/l), reversed the inhibition of osteoclastic bone resorption induced by high extracellular Ca2+ (15 mM). The IL-6 effect was abrogated by excess soluble IL-6 receptor (500 μg/l). Additionally, IL-6 (5 pg/l to 10 μg/l) inhibited cytosolic Ca2+ signals triggered by high Ca2+ or Ni2+. In separate experiments, osteoclasts incubated in 10 mM Ca2+ or on bone released more IL-6 than those in 1.25 mM Ca2+. Furthermore, IL-6 mRNA histostaining was more intense in osteoclasts in 10 or 20 mM Ca2+ than cells in 1.25 mM Ca2+. Similarly, IL-6 receptor mRNA histostaining was increased in osteoclasts incubated in 5 or 10 mM Ca2+. Thus, while high Ca2+ enhances IL-6 secretion, the released IL-6 attenuates Ca2+ sensing and reverses inhibition of resorption by Ca2+. Such an autocrine-paracrine loop may sustain osteoclastic activity in the face of an inhibitory Ca2+ level generated locally during resorption.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.142.5.1347