Differential regulation of cadherins by dexamethasone in human osteoblastic cells

Fernando Lecanda, Su Li Cheng, Chan Soo Shin, Mari K. Davidson, Pamela Warlow, Louis V. Avioli, Roberto Civitelli

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Human osteoblasts express a repertoire of cadherins, including N- cadherin (N-cad), cadherin-11 (C11), and cadherin-4 (C4). We have previously shown that direct cell-cell adhesion via cadherins is critical for BMP-2- induced osteoblast differentiation. In this study, we have analyzed the regulation of cadherin expression in normal human trabecular bone osteoblasts (HOB), and osteoprogenitor marrow stromal cells (BMC), during exposure to dexamethasone, another inducer of human bone cell differentiation. Dexamethasone inhibited the expression of both C11 and N-cad mRNA in both BMC and HOB, although the effect was much more pronounced on N-cad than on C11. This action of the steroid was dose dependent, was maximal at 10-7 M concentration, and occurred as early as after 1 day of incubation. By contrast, expression of C4 mRNA and protein was strongly induced by dexamethasone in BMC and was stimulated in HOB. This stimulatory effect lasted for at least 2 weeks of incubation. A cadherin inhibitor, HAV- containing decapeptide only partially (~50%) prevented dexamethasone-induced stimulation of alkaline phosphatase activity by BMC, which instead was not altered by incubation with a neutralizing antibody against C4. Therefore, the pattern of cadherin regulation by dexamethasone radically differs form that observed with BMP-2. Dexamethasone effects on certain osteoblast differentiated features, such as induction of alkaline phosphatase activity are not strictly dependent on cadherin function. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)499-506
Number of pages8
JournalJournal of cellular biochemistry
Volume77
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Cadherins
  • Cell-cell adhesion
  • Corticosteroids
  • Hormonal regulation
  • Osteoblast differentiation

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