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The glutamate receptor antagonist MK801 modulates bone resorption in vitro by a mechanism predominantly involving osteoclast differentiation
Author(s) -
PEET NICKY M.,
GRABOWSKI PETER S.,
LAKETIćLJUBOJEVIć IRA,
SKERRY TIM M.
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.15.2179
Subject(s) - osteoclast , bone resorption , glutamate receptor , chemistry , resorption , endocrinology , nmda receptor , agonist , medicine , microbiology and biotechnology , receptor , antagonist , biology , biochemistry
Recent identification in bone of transporters, receptors, and components of synaptic signaling suggests a role for glutamate in the skeleton. We investigated effects of glutamate and its antagonist MK801 on osteoclasts in vitro. Glutamate applied to patch clamped osteoclasts induced significant increases in whole‐cell membrane currents ( P <0.01) in the presence of the coagonist glycine. Agonist‐elicited currents were significantly decreased after application of MK801 (100 µM, P <0.01), butMK801 had no effect on actin ring formation necessary for osteoclast polarization, attachment, and resorption. In cocultures of bone marrow cells and osteoblasts in which osteoclasts develop, MK801 inhibited osteoclast differentiation and reduced resorption of pits in dentine (3 to 100 µM; P <0.001). MK801 added early in the culture (for as little as 2–4 days) was as effective as addition for the entire culture period. Addition of MK801 for any time after day 7 of culture was ineffective in reducing osteoclast activity. Using rat and rabbit mature osteoclasts cultured on dentine or explants of mouse calvariae prelabeled with 45 Ca, we could not detect significant effects of MK801 on osteoclastic resorption. These data show clearly that glutamate receptor function is critical during osteoclastogenesis and suggest that glutamate is less important in regulating mature osteoclast activity.—Peet, N. M., Grabowski, P. S., Laketić‐Ljubojević, I., Skerry, T. M. The glutamate receptor antagonist MK801 modulates bone resorption in vitro by a mechanism predominantly involving osteoclast differentiation. FASEB J. 13, 2179–2185 (1999)