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-LJUBOJEVIDepartment of Biology, University of York, York, YO10 5YW, U.K.
1Correspondence: Department of Biology, University of York, PO Box 373, York, YO10 5YW, U.K. E-mail nmp2{at}york.ac.uk
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), but MK801 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 45Ca, 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., Laketi
-Ljubojevi, I., Skerry, T. M. The
glutamate receptor antagonist MK801 modulates bone resorption in
vitro by a mechanism predominantly involving osteoclast
differentiation.
Key Words: osteoclast • differentiation • electrophysiology • glutamate receptor • MK801 maleate (Dizocilpine)
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