Differential regulation of cadherins by dexamethasone in human osteoblastic cells

✍ Scribed by Fernando Lecanda; Su-Li Cheng; Chan Soo Shin; Mari K. Davidson; Pamela Warlow; Louis V. Avioli; Roberto Civitelli

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 195 KB
• Volume: 77
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(20000601)77:3<499::aid-jcb14>3.0.co;2-0

✦ Synopsis

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-2induced 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 Ϫ7 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 (ϳ50%) 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.