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Regulation of connexin43 expression and function by prostaglandin E 2 (PGE 2 ) and parathyroid hormone (PTH) in osteoblastic cells
Author(s) -
Civitelli Roberto,
Ziambaras Konstantinos,
Warlow Pamela M.,
Lecanda Fernando,
Nelson Tracy,
Harley James,
Atal Namita,
Beyer Eric C.,
Steinberg Thomas H.
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19980101)68:1<8::aid-jcb2>3.0.co;2-#
Subject(s) - parathyroid hormone , forskolin , gap junction , prostaglandin e2 , medicine , endocrinology , cycloheximide , stimulation , intracellular , connexin , chemistry , transfection , extracellular , cell culture , microbiology and biotechnology , biology , protein biosynthesis , calcium , genetics
Connexin43 (Cx43) forms gap junctions that mediate intercellular communication between osteoblasts. We have examined the effects of prostaglandin E 2 (PGE 2 ) and parathyroid hormone (PTH) on gap junctional communication in the rat osteogenic sarcoma cells UMR 106‐01. Incubation with either PGE 2 or PTH rapidly (within 30 min) increased transfer of negatively charged dyes between UMR 106‐01 cells. This stimulatory effect lasted for at least 4 h. Both PGE 2 and PTH increased steady‐state levels of Cx43 mRNA, but only after 2–4 h of incubation. Transfection with a Cx43 gene construct linked to luciferase showed that this effect of PTH was the result of transcriptional upregulation of Cx43 promoter. Stimulation of dye coupling and Cx43 gene transcription were reproduced by forskolin and 8Br‐cAMP. Exposure to PGE 2 for 30 min increased Cx43 abundance at appositional membranes in UMR 106‐01, whereas total Cx43 protein levels increased only after 4–6 h of incubation with either PGE 2 or PTH. Inhibition of protein synthesis by cycloheximide did not affect this early stimulation of dye coupling, but it significantly inhibited the sustained effect of PTH and forskolin on cell coupling. In summary, both PTH and PGE 2 , presumably through cAMP production, enhance gap junctional communication in osteoblastic cell cultures via two mechanisms: initial rapid redistribution of Cx43 to the cell membrane, and later stimulation of Cx43 gene expression. Modulation of intercellular communication represents a novel mechanism by which osteotropic factors regulate the activity of bone forming cells. J. Cell. Biochem. 68:8–21, 1998. © 1998 Wiley‐Liss, Inc.