INTERACTION OF TRIIODOTHYRONINE WITH 1-ALPHA,25-DIHYDROXYVITAMIN D-3 ON INTERLEUKIN-6-DEPENDENT OSTEOCLAST-LIKE CELL-FORMATION IN MOUSE BONE-MARROW CELL-CULTURES

In mouse bone marrow cultures, the formation of osteoclastlike, that i s, tartrate-resistant acid phosphatase-positive (TRAP(+)) and calciton in (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 betwe en 10(-11) and 10(-8) mol/L T-3. Importantly, inhibition of prostaglan din synthesis by indomethacin significantly impeded osteoclast-like ce ll formation by 1 alpha,25(OH)(2)D-3 and abrogated the effect of T-3 t hereon, Basal interleukin-6 (IL-6) production by cultured marrow cells was significantly stimulated by 1 alpha,25(OH)(2)D-3. However, even a t 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 sti mulatory effect of 1 alpha,25(OH)(2)D-3 on osteoclastogenesis was part ially 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 throug h the IL-6/IL-6R system is also a prerequisite for the auxiliary effec t 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 ac tion, which is also subject to modulation by T-3, The mechanism of int eraction of the two hormones apparently involves joint stimulation of prostaglandin synthesis. (C) 1998 by Elsevier Science Inc, All rights reserved.