title: Interaction of triiodothyronine with 1alpha,25-dihydroxyvitamin D3 on interleukin-6-dependent osteoclast-like cell formation in mouse bone marrow cell cultures.
abstract: In mouse bone marrow cultures, the formation of osteoclast-like, that is, tartrate-resistant acid phosphatase-positive (TRAP+) and calcitonin (CT) receptor-positive multinucleated cells (MNCs), induced by 10(-10) to 10(-8) mol/L 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], could be augmented by triiodothyronine (T3), which alone had no effect on osteoclast-like cell formation. The permissive effect of T3 increased the response to 1alpha,25(OH)2D3 by approximately one order of magnitude. Linear concentration dependence was observed between 10(-11) and 10(-8) mol/L T3. Importantly, inhibition of prostaglandin synthesis by indomethacin significantly impeded osteoclast-like cell formation by 1alpha,25(OH)2D3 and abrogated the effect of T3 thereon. Basal interleukin-6 (IL-6) production by cultured marrow cells was significantly stimulated by 1alpha,25(OH)2D3. However, even at an exceedingly high concentration of 20 ng/mL, IL-6 was ineffective in inducing osteoclast-like cell formation. Therefore, any hormonally induced rise in IL-6 release from bone marrow cells could not account for the observed changes in TRAP+ MNC numbers. Nevertheless, the stimulatory effect of 1alpha,25(OH)2D3 on osteoclastogenesis was partially dependent on IL-6 because it could be significantly blocked by a neutralizing monoclonal anti-IL-6 antibody, and to the same extent by a monoclonal anti-IL-6 receptor antibody. Unimpaired signaling through the IL-6/IL-6R system is also a prerequisite for the auxiliary effect of T3 on induction of osteoclast-like cells by 1alpha,25(OH)2D3. Our data provide evidence that 1alpha,25(OH)2D3 induces osteoclast-like cell formation, at least in part, in an IL-6-dependent mode of action, which is also subject to modulation by T3. The mechanism of interaction of the two hormones apparently involves joint stimulation of prostaglandin synthesis.
authors.affiliation: Department of General and Experimental Pathology, University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Schiller
authors.forename: R
authors.initials: R
authors.lastname: Gruber
authors.forename: G M
authors.initials: GM
authors.lastname: Ho
authors.forename: K
authors.initials: K
authors.lastname: Redlich
authors.forename: H J
authors.initials: HJ
authors.lastname: Gober
authors.forename: F
authors.initials: F
authors.lastname: Katzgraber
authors.forename: M
authors.initials: M
authors.lastname: Willheim
authors.forename: O
authors.initials: O
authors.lastname: Hoffmann
authors.forename: P
authors.initials: P
authors.lastname: Pietschmann
authors.forename: M
authors.initials: M
authors.lastname: Peterlik
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015726:Giant Cells / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000166:cytology*; D011453:Prostaglandins / Q000096:biosynthesis; D018003:Receptors, Calcitonin / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D007527:Isoenzymes; D011453:Prostaglandins; D018003:Receptors, Calcitonin; D014284:Triiodothyronine; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol