title: Differential regulation of cadherins by dexamethasone in human osteoblastic cells.
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 ( approximately 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.
authors.affiliation: Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: F
authors.initials: F
authors.lastname: Lecanda
authors.forename: S L
authors.initials: SL
authors.lastname: Cheng
authors.forename: C S
authors.initials: CS
authors.lastname: Shin
authors.forename: M K
authors.initials: MK
authors.lastname: Davidson
authors.forename: P
authors.initials: P
authors.lastname: Warlow
authors.forename: L V
authors.initials: LV
authors.lastname: Avioli
authors.forename: R
authors.initials: R
authors.lastname: Civitelli
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015152:Blotting, Northern; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D015820:Cadherins / Q000096:biosynthesis*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010455:Peptides / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta
chemical_list: D018931:Antineoplastic Agents, Hormonal; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D015820:Cadherins; D010455:Peptides; C083970:R-cadherin; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C086960:osteoblast cadherin; D003907:Dexamethasone; D000469:Alkaline Phosphatase