IN-VITRO PRODUCTION OF CYTOKINES BY BONE SURFACE-DERIVED OSTEOBLASTICCELLS IN NORMAL AND OSTEOPOROTIC POSTMENOPAUSAL WOMEN - RELATIONSHIP WITH CELL-PROLIFERATION

To evaluate the role of cytokines produced by osteoblasts in the patho physiology of bone lesions in postmenopausal osteoporosis (PMOP), we h ave determined by RIA and immunoradiometric assays the levels of prost aglandin E2 (PGE2), interleukin-1beta (IL-1), tumor necrosis factor-al pha (TNFalpha), and IL-6 released by cultured bone surface-derived ost eoblastic (OB) cells isolated from 24 untreated PMOP women with high, low, or normal bone turnover on bone biopsy. OB cells isolated from pa tients with high bone formation had a 2-fold increased proliferation r ate in vitro compared to OB cells from patients with normal or low bon e formation or OB cells from age-matched controls. The spontaneous in vitro production per cell protein of PGE2, IL-1, and TNFalpha, but not of IL-6, was 2- to 3-fold lower in rapidly proliferating OB cells iso lated from PMOP patients with high bone formation compared to OB cells from patients with normal or low proliferation or control cells. Trea tment with 10 nmol/L 1,25-dihydroxyvitamin D (48 h) increased PGE2 lev els to normal values in OB cells with a high proliferation rate, but d ecreased PGE, production in cells with low proliferation and in contro l cells, suggesting that the release of PGE2 was dependent on the stag e of maturation of OB cells. Significant correlations were found betwe en IL-1 and TNFalpha (r = 0.87; P < 0.001), IL-1 and PGE2 (r = 0.46; P < 0.05), IL-6 and IL-1 (r = 0.39; P < 0.05), and IL-6 and TNFalpha (r = 0.49; P < 0.05), suggesting that the production of these cytokines was under reciprocal control. The results indicate that the in vitro p roduction of PGE2, IL-1, and TNFalpha, but not IL-6, by OB cells isola ted from patients with PMOP is related to the proliferation rate of th ese cells and the rate of bone formation. The variable production of c ytokines by OB cells may contribute to the histological heterogeneity of bone formation in PMOP.