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Regulation of cytoplasmic calcium concentration in tetracycline‐treated osteoclasts
Author(s) -
Donahue Henry J.,
Iijima Kazumoto,
Goligorsky Michael S.,
Rubin Clinton T.,
Rifkin Barry R.
Publication year - 1992
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 - 10.1002/jbmr.5650071111
Subject(s) - osteoclast , extracellular , minocycline , cytosol , bone resorption , chemistry , calcium , doxycycline , bone remodeling , microbiology and biotechnology , intracellular , calcium metabolism , resorption , ionomycin , endocrinology , medicine , biochemistry , in vitro , biology , organic chemistry , enzyme , antibiotics
The ability of low‐dose tetracyclines to inhibit collagenase activity and inactivate osteoclasts suggests that these compounds have great potential as a prophylaxis for metabolic bone disease. However, the cellular mechanism by which tetracyclines interact with skeletal tissue is not yet clear. To better understand the effects of tetracyclines on bone metabolism, we examined their effect on osteoclast activity in vitro. Because tetracyclines can enter the cell and bind calcium and have been reported to directly interact with osteoclasts, we postulated that exposure to either of two tetracyclines, minocycline or doxycycline, would alter cytosolic Ca 2+ regulation in rat osteoclasts. [Ca 2+ ] i was measured in single rat osteoclasts utilizing fura‐2. Addition of extracellular Ca 2+ (5 mM CaCl 2 ), a potent osteoclast inhibitor, increased [Ca 2+ ] i in all osteoclasts, but 10 −6 M salmon calcitonin (sCT) did so only in a subpopulation of osteoclasts. Neither minocycline nor doxycycline (10 μg/ml) altered steady‐state osteoclast [Ca 2+ ] i . Further, neither minocycline nor doxycycline pretreatment affected the sCT‐mediated increases in [Ca 2+ ] i . However, tetracycline pretreatment significantly decreased the cytosolic Ca 2+ response to extracellular CaCl 2 . Our results strongly suggest that tetracyclines have a specific effect on extracellular Ca 2+ ‐stimulated cytosolic Ca 2+ mobilization in osteoclasts, which is not solely dependent on their ability to buffer Ca 2+ . Furthermore, these results point to the potential use of tetracyclines as probes to study cytosolic Ca 2+ regulation. However, that tetracyclines attenuate a signal response associated with decreased osteoclastic resorption suggests that the reported antiresorptive attributes of tetracyclines must be achieved independently of an effect on osteoclastic cytosolic Ca 2+ .