{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:17:44Z","timestamp":1790770664377,"version":"4.1.0"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,9,7]]},"abstract":"<jats:p>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\u2013 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 \u03bcg\/l), but not IL-11 (10 and 100 \u03bcg\/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 \u03bcg\/l). Additionally, IL-6 (5 pg\/l to 10 \u03bcg\/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\u2013paracrine loop may sustain osteoclastic activity in the face of an inhibitory Ca2+ level generated locally during resorption.<\/jats:p>","DOI":"10.1083\/jcb.142.5.1347","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:47:50Z","timestamp":1027702070000},"page":"1347-1356","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["Mode of Action of Interleukin-6 on Mature Osteoclasts. Novel Interactions with Extracellular Ca2+ Sensing in the Regulation of Osteoclastic Bone Resorption"],"prefix":"10.1083","volume":"142","author":[{"given":"Olugbenga A.","family":"Adebanjo","sequence":"first","affiliation":[{"name":"*Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, and Department of Medicine, Medical College of Pennsylvania\u2013Hahnemann School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and \u00a7School of Dentistry, University of Southern California, Los Angeles, California 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baljit S.","family":"Moonga","sequence":"additional","affiliation":[{"name":"*Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, and Department of Medicine, Medical College of Pennsylvania\u2013Hahnemann School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and \u00a7School of Dentistry, University of Southern California, Los Angeles, California 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoo","family":"Yamate","sequence":"additional","affiliation":[{"name":"*Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, and Department of Medicine, Medical College of Pennsylvania\u2013Hahnemann School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and \u00a7School of Dentistry, University of Southern California, Los Angeles, California 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"*Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, and Department of Medicine, Medical College of Pennsylvania\u2013Hahnemann School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and \u00a7School of Dentistry, University of Southern California, Los Angeles, California 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Minkin","sequence":"additional","affiliation":[{"name":"*Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, and Department of Medicine, Medical College of Pennsylvania\u2013Hahnemann School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and \u00a7School of Dentistry, University of Southern California, Los Angeles, California 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuko","family":"Abe","sequence":"additional","affiliation":[{"name":"*Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, and Department of Medicine, Medical College of Pennsylvania\u2013Hahnemann School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and \u00a7School of Dentistry, University of Southern California, Los Angeles, California 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mone","family":"Zaidi","sequence":"additional","affiliation":[{"name":"*Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, and Department of Medicine, Medical College of Pennsylvania\u2013Hahnemann School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and \u00a7School of Dentistry, University of Southern California, Los Angeles, California 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