Interaction of triiodothyronine with 1α, 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 1α,25-dihydroxyvitamin D 3 [1α,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 1α,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 1α,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 1α,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 1α,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 1α,25(OH) 2 D 3 . Our data provide evidence that 1α,25(OH) 2 D 3 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.