Gap-junctional communication mediates parathyroid hormone stimulation of mineralization in osteoblastic cultures

Previously we showed that physiological levels of parathyroid hormone (PTH) can increase the mineralization of extracellular matrix (ECM) by osteoblas t-like cells in vitro. In this study, we assess the role of gap-junctional intercellular communication (GJC) in the PTH-enhanced mineralization of ECM in MC3T3-E1 cells, a murine culture model of osteoblastic differentiation. Messenger RNA and protein for connexin 43 (Cx43), the major component of M C3T3-E1 gap junctions, and GJC increased as the cells progressed toward a m ature phenotype, Immunocytochemistry showed accumulation of Cx43 at the are a of close contact between cells. The timing of the PTH treatment that incr eased matrix mineralization in these cells coincided with the highest expre ssion of Cx43 and GJC, Administration of 18-alpha -glycyrrhetinic acid (AGA ) promptly blocked GJC in cultures of MC3T3-E1 cells in a dose-dependent an d reversible manner at all times tested during the culture period. Treatmen t with AGA, but not with an inactive analog, reversed the PTH-induced ECM m ineralization, These data suggest that GJC mediates anabolic actions of PTH related to osteoblast-mediated mineralization. (C) 2001 by Elsevier Scienc e Inc. All rights reserved.