Retinoic acid suppresses interleukin 6 production in normal human osteoblasts

Systemic long-term retinoid therapy for chronic skin diseases significantly reduced bone turnover markers within days and led to bone abnormalities, R etinoic acid (RA) plays a key role in the regulation of mouse bone cell pro liferation, differentiation and functions. Meanwhile, there is little infor mation of RA effect on human osteoblast and osteoclast cell development and function. Interleukin 6 (IL-6) is a pleiotropic cytokine with profound eff ects on bone metabolism, Thus, the present study examined the RA effect on cell differentiation, alkaline phosphatase and osteocalcin production as we ll as IL-6 production in normal human osteoblasts, The number of large diff erentiated osteoblast cells decreased in RA-treated cultures P<0.05. The pr oduction of bone specific markers, alkaline phosphatase and osteocalcin, wa s also reduced in RA-treated cultures. Normal human osteoblasts produced 31 .0 +/- 4.8 pg IL-6 per mi in control cultures, Within 24 h, RA at all four concentrations reduced Il-6 production from normal human osteoblasts, The p harmacological concentration of 10(-5) M RA suppressed 90% of IL-6 producti on. The present study shows for the first time that RA profoundly inhibits IL-6 production in normal human osteoblasts within 24 h and in a dose-depen dent manner. RA was shown previously to inhibit IL-6 production in several other normal and malignant human cell types, The associated decrease in ost eoblast cell differentiation, alkaline phosphatase and osteocalcin producti on could result from the rapid RA-inhibition of IL-6 production. Thus, RA i nhibition of IL-6 production in normal human osteoblasts may contribute to the bone abnormalities seen after systemic long-term retinoid therapy in so me patients. (C) 2000 Academic Press.