Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation

S. U.L.I. Cheng, Fernando Lecanda, Mari K. Davidson, Pamela M. Warlow, Shu Fang Zhang, Liming Zhang, Shintaro Suzuki, Tom S.T. John, Roberto Civitelli

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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.

Original languageEnglish
Pages (from-to)633-644
Number of pages12
JournalJournal of Bone and Mineral Research
Volume13
Issue number4
DOIs
StatePublished - Apr 1 1998

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    Cheng, S. U. L. I., Lecanda, F., Davidson, M. K., Warlow, P. M., Zhang, S. F., Zhang, L., Suzuki, S., John, T. S. T., & Civitelli, R. (1998). Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation. Journal of Bone and Mineral Research, 13(4), 633-644. https://doi.org/10.1359/jbmr.1998.13.4.633