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Dual Mechanism of Intercellular Communication in HOBIT Osteoblastic Cells: A Role for Gap‐Junctional Hemichannels
Author(s) -
Romanello Milena,
D'Andrea Paola
Publication year - 2001
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2001.16.8.1465
Subject(s) - gap junction , intracellular , lucifer yellow , paracrine signalling , microbiology and biotechnology , extracellular , thapsigargin , cell signaling , apyrase , biology , chemistry , signal transduction , biochemistry , receptor
Intercellular communication allows tissue coordination of cell metabolism and sensitivity to extracellular stimuli. Paracrine stimulation and cell‐to‐cell coupling through gap junctions induce the formation of complex cellular networks, which favors the intercellular exchange of nutrients and second messengers. Intercellular Ca 2+ signaling was investigated in human osteoblast‐like initial transfectant (HOBIT) cells, a human osteoblastic cell line in which cells retain most of the osteoblastic differentiation markers. HOBIT cells express connexin43 (Cx43) clustered at the cell‐to‐cell boundary and display functional intercellular coupling as assessed by the intercellular transfer of Lucifer yellow. Mechanical stimulation of a single cell induced a wave of increased Ca 2+ that was radially propagated to surrounding cells. Treatment of cells with thapsigargin blocked mechanically induced signal propagation. Intercellular Ca 2+ spreading and dye transfer were inhibited by 18α‐glycyrrhetinic acid (18‐GA), showing the involvement of gap junctions in signal propagation. Pretreatment of cells with suramin or with apyrase decreased the extent of wave propagation, suggesting that ATP‐mediated paracrine stimulation contribute to cell‐to‐cell signaling. The functional expression of gap‐junctional hemichannels was evidenced in experiments of Mn 2+ quenching, extracellular dye uptake, and intracellular Ca 2+ release, activated by uptake of inositol 1,4,5‐trisphosphate (InsP 3 ) from the external medium. Gap‐junctional hemichannels were activated by low extracellular Ca 2+ concentrations and inhibited by 18‐GA. A role for Cx hemichannels in adenosine triphosphate (ATP) release and paracrine stimulation is suggested.