Human Osteoblasts Express a Repertoire of Cadherins, Which Are Critical for BMP‐2–Induced Osteogenic Differentiation

Abstract

Direct cell–cell interactions are fundamental for tissue development and differentiation. We have studied the expression and function of cadherins in human osteoblasts during in vitro differentiation. Using reverse transcription‐polymerase chain reaction and mRNA hybridization, we found that human trabecular bone osteoblasts (HOBs), osteoprogenitor marrow stromal cells (BMCs), and the osteogenic sarcoma lines, SaOS‐2 and MG‐63, expressed mRNA for cadherin‐11 (C11) and N‐cadherin (N‐cad). HOBs and BMCs also expressed low levels of cadherin‐4 (C4) mRNA. C11 was the most abundant cadherin protein present in human osteoblasts, and its expression was unaffected by bone morphogenetic protein‐2 (BMP‐2) treatment of either BMCs or HOBs. Likewise, N‐cad mRNA did not change during BMP‐2 incubation. Conversely, C4 protein, undetectable in transformed cell lines, was down‐regulated by BMP‐2 treatment of normal cells. Both C11 and C4 were localized to sites of cell–cell contact in both HOBs and BMCs, colocalized with β‐catenin, and bands corresponding to cadherins were coimmunoprecipitated by a β‐catenin antibody, findings indicative of functional cadherins. A decapeptide containing the HAV motif of human N‐cad partially inhibited Ca²⁺‐dependent cell–cell adhesion and completely prevented BMP‐2–induced stimulation of alkaline phosphatase activity by BMCs. Thus, human osteoblasts and their progenitor cells express a repertoire of multiple cadherins. Cadherin‐mediated cell‐to‐cell adhesion is critical for normal human osteoblast differentiation.