Interaction of triiodothyronine with 1α,25-dihydroxyvitamin D3 on interleukin-6-dependent osteoclast-like cell formation in mouse bone marrow cell cultures

In mouse bone marrow cultures, the formation of osteoclastlike, 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 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3], could be augmented by triiodothyronine (T-3), which alone had no effect on osteoclast-like cell formation, The permissive effect of T-3 increased the response to 1 alpha,25(OH)(2)D-3 by approximately one order of magnitude, Linear concentration dependence was observed between 10(-11) and 10(-8) mol/L T-3. Importantly, inhibition of prostaglandin synthesis by indomethacin significantly impeded osteoclast-like cell formation by 1 alpha,25(OH)(2)D-3 and abrogated the effect of T-3 thereon, Basal interleukin-6 (IL-6) production by cultured marrow cells was significantly stimulated by 1 alpha,25(OH)(2)D-3. 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 1 alpha,25(OH)(2)D-3 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 T-3 on induction of osteoclast-like cells by 1 alpha,25(OH)(2)D-3, Our data provide evidence that 1 alpha,25(OH),D, induces osteoclast-like cell formation, at least in part, in an IL-6-dependent mode of action, which is also subject to modulation by T-3, The mechanism of interaction of the two hormones apparently involves joint stimulation of prostaglandin synthesis. (C) 1998 by Elsevier Science Inc, All rights reserved.