A dominant negative cadherin inhibits osteoblast differentiation

Su Li Cheng, Chan Soo Shin, Dwight A. Towler, Roberto Civitelli

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

We have previously indicated that human osteoblasts express a repertoire of cadherins and that perturbation of cadherin-mediated cell-cell interaction reduces bone morphogenetic protein 2 (BMP-2) stimulation of alkaline phosphatase activity. To test whether inhibition of cadherin function interferes with osteoblast function, we expressed a truncated N-cadherin mutant (NCad:C) with dominant negative action in MC3T3-E1 osteoblastic cells. In stably transfected clones, calcium-dependent cell-cell adhesion was decreased by 50%. Analysis of matrix protein expression during a 4-week culture period revealed that bone sialoprotein, osteocalcin, and type I collagen were substantially inhibited with time in culture, whereas osteopontin transiently increased. Basal alkaline phosphatase activity declined in cells expressing NCad:C, relative to control cells, after 3 weeks in culture, and their cell proliferation rate was reduced moderately (17%). Finally, 45Ca uptake, an index of matrix mineralization, was decreased by 35% in NCad:C-expressing cells compared with control cultures after 4 weeks in medium containing ascorbic acid and β-glycerophosphate. Similarly, BMP-2 stimulation of alkaline phosphatase activity and bone sialoprotein and osteopontin expression also were curtailed in NCad:C cells. Therefore, expression of dominant negative cadherin results in decreased cell-cell adhesion associated with altered bone matrix protein expression and decreased matrix mineralization. Cadherin-mediated cell-cell adhesion is involved in regulating the function of bone-forming cells.

Original languageEnglish (US)
Pages (from-to)2362-2370
Number of pages9
JournalJournal of Bone and Mineral Research
Volume15
Issue number12
DOIs
StatePublished - Dec 2000

Keywords

  • Bone formation
  • Cadherin
  • Cell adhesion molecules
  • Osteoblast differentiation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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