Hypothesis/Objective: Otosclerosis is a bone remodeling disorder localized to the otic capsule and associated with inflammation. In vitro, increased activity of the diastrophic dysplasia sulf/te transporter (DTDST), which is implicated in bone metabolism, has been reported. Because glucocorticoids modulate the bone turnover and inhibit inflammatory processes, we investigated the effect of dexamethasone (Dex) on interleukin-6 and DTDST in otosclerosis.
Study Design: The authors conducted a prospective, case–control study.
Materials and Methods: Primary cell cultures were obtained from stapes and external auditory canals in otosclerosis (n = 21) and control patients (n = 18). Assays with [3H]Dex evaluated specific binding sites in otosclerotic and control stapes. The effects of Dex (10−9 to 10−6 M) and RU486 (10−7 M), a glucocorticoid antagonist, were studied on DTDST activity by sulfate uptake. IL-6 secretion was measured in culture media before and after Dex (10−7 M, 24 hours). The effect of IL-6 (10−7 M, 24 hours) was assessed on DTDST activity in control stapes.
Results: The number of specific Dex-binding sites was similar in all stapedial cultures. Dex inhibited DTDST activity (19.4 ± 1.02 vs. 29.4 ± 3.94 pmol/μg prot/5 minutes) only in otosclerotic stapes. This effect was dose-dependent, antagonized by RU 486 and only observed 24 hours after Dex exposure. Interleukin (IL)-6 stimulated DTDST activity in normal stapes, whereas Dex inhibited IL-6 production only in otosclerotic stapes.
Conclusion: Dex inhibits the DTDST activity, at least in part, through a reduction of IL-6 secretion only in otosclerotic cells. This effect is mediated through the glucocorticoid receptors and may lead to the reduction of bone turnover.