Gap junctional communication modulates gene expression in osteoblastic cells

Fernando Lecanda, Dwight A. Towler, Konstantinos Ziambaras, Su Li Cheng, Michael Koval, Thomas H. Steinberg, Roberto Civitelli

Research output: Contribution to journalArticle

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Abstract

Bone-forming cells are organized in a multicellular network interconnected by gap junctions. In these cells, gap junctions are formed by connexin43 (Cx43) and connexin45 (Cx45). Cx43 gap junctions form pores that are more permeable to negatively charged dyes such as Lucifer yellow and calcein than are Cx45 pores. We studied whether altering gap junctional communication by manipulating the relative expression of Cx43 and Cx45 affects the osteoblast phenotype. Transfection of Cx45 in cells that express primarily Cx43 (ROS 17/2.8 and MC3T3-E1) decreased both dye transfer and expression of osteocalcin (OC) and bone sialoprotein (BSP), genes pivotal to bone matrix formation and calcification. Conversely, transfection of Cx43 into cells that express predominantly Cx45 (UMR 106-01) increased both cell coupling and expression of OC and BSP. Transient cotransfection of promoter- luciferase constructs and connexin expression vectors demonstrated that OC and BSP gene transcription was down-regulated by Cx45 cotransfection in ROS 17/2.8 and MC3T3-E1 cells, in association with a decrease in dye coupling. Conversely, cotransfection of Cx43 in UMR 106-01 cells up-regulated OC and BSP gene transcription. Activity of other less specific osteoblast promoters, such as osteopontin and osteonectin, was less sensitive to changes in gap junctional communication. Thus, altering gap junctional permeability by manipulating the expression of Cx43 and Cx45 in osteoblastic cells alters transcriptional activity of osteoblast-specific promoters, presumably via modulation of signals that can diffuse from cell to cell. A communicating intercellular network is required for the full elaboration of a differentiated osteoblastic phenotype.

Original languageEnglish (US)
Pages (from-to)2249-2258
Number of pages10
JournalMolecular Biology of the Cell
Volume9
Issue number8
DOIs
StatePublished - Jan 1 1998

Fingerprint

Connexin 43
Gene Expression
Integrin-Binding Sialoprotein
Osteocalcin
Gap Junctions
Osteoblasts
Coloring Agents
Transfection
Osteonectin
Genes
Phenotype
Bone Matrix
Osteopontin
Connexins
Intercellular Junctions
Luciferases
Osteogenesis
Permeability
Bone and Bones

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Lecanda, F., Towler, D. A., Ziambaras, K., Cheng, S. L., Koval, M., Steinberg, T. H., & Civitelli, R. (1998). Gap junctional communication modulates gene expression in osteoblastic cells. Molecular Biology of the Cell, 9(8), 2249-2258. https://doi.org/10.1091/mbc.9.8.2249

Gap junctional communication modulates gene expression in osteoblastic cells. / Lecanda, Fernando; Towler, Dwight A.; Ziambaras, Konstantinos; Cheng, Su Li; Koval, Michael; Steinberg, Thomas H.; Civitelli, Roberto.

In: Molecular Biology of the Cell, Vol. 9, No. 8, 01.01.1998, p. 2249-2258.

Research output: Contribution to journalArticle

Lecanda, F, Towler, DA, Ziambaras, K, Cheng, SL, Koval, M, Steinberg, TH & Civitelli, R 1998, 'Gap junctional communication modulates gene expression in osteoblastic cells', Molecular Biology of the Cell, vol. 9, no. 8, pp. 2249-2258. https://doi.org/10.1091/mbc.9.8.2249
Lecanda, Fernando ; Towler, Dwight A. ; Ziambaras, Konstantinos ; Cheng, Su Li ; Koval, Michael ; Steinberg, Thomas H. ; Civitelli, Roberto. / Gap junctional communication modulates gene expression in osteoblastic cells. In: Molecular Biology of the Cell. 1998 ; Vol. 9, No. 8. pp. 2249-2258.
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