Parathyroid hormone up-regulation of connexin 43 gene expression in osteoblasts depends on cell phenotype

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Abstract

Accumulating evidence indicates that gap junctions, primarily composed of connexin 43 (Cx43), are distributed extensively throughout bone. We have previously reported that in osteoblastic cells parathyroid hormone (PTH) increases both the steady-state levels of transcripts for Cx43 and gap- junctional intercellular communication in a process involving cyclic adenosine monophosphate (cAMP). We now present data showing that the mechanism of stimulation of Cx43 gene expression by PTH involves an increased rate of Cx43 gene transcription without affecting Cx43 transcript stability in UMR 106 osteoblastic cells. Activation of the protein kinase C pathway is not involved in this process. Inhibiting translation consistently decreases the PTH-mediated stimulation of Cx43 gene expression at all the times we tested (1-3 h). However, this effect is only partial, demonstrating that de novo protein synthesis is required for full stimulation. PTH increases the steady-state levels of Cx43 mRNA in several osteoblastic cell lines, albeit to different levels. We were unable to detect PTH stimulation in ROS 17/2.8 osteoblastic cells, suggesting that the effect of PTH on Cx43 gene expression may depend on the developmental state of the cell along the osteoblastic differentiation pathway. In the MC3T3-E1 preosteoblastic cell line, we find that PTH increases Cx43 gene expression in proliferating and maturing osteoblastic cells, but not in nondividing, differentiated osteoblasts, where the basal level of Cx43 gene expression is elevated: Unlike PTH, the osteotropic hormones 1,25-dihydroxyvitamin D3 and 17β-estradiol do not appear to affect Cx43 gene expression in UMR 106 osteoblastic cells.

Original languageEnglish (US)
Pages (from-to)2005-2013
Number of pages9
JournalJournal of Bone and Mineral Research
Volume12
Issue number12
DOIs
StatePublished - Dec 1997

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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