Integrin receptor-mediated mobilisation of intranuclear calcium in rat osteoclasts.
Cell-matrix interactions have been shown to play an important role in regulating cell function and behaviour. In bone, where calcified matrix formation and resorption events are required to be in dynamic equilibrium, regulation of adhesive interactions between bone cells and their matrix is critical. The present study focuses on the osteoclast, the bone resorbing cell, as well as integrins, which are cell surface adhesion receptors that mediate osteoclast attachment to bone matrix. In osteoclasts, the most abundant integrin receptor is the vitronectin receptor (VNR, alpha v beta 3). The objective of the study was to investigate changes in intracellular calcium, a regulator of osteoclast function, following addition of peptides that bind integrins, in particular the alpha v beta 3 form of the vitronectin receptor (VNR), which is highly expressed in osteoclasts. The study demonstrated a unique spatial localisation of the calcium signal in response to cell membrane receptor occupancy by integrin ligands in rat osteoclasts. Addition of peptides with the Arg-Gly-Asp (RGD) sequence such as BSP-IIA, GRGDSP and GRGDS to rat osteoclasts evoked an immediate increase in free calcium ion concentration [Ca2+]i, localised to the nuclei and to the thin cytoplasmic skirt. These responses were inhibited by F11, a monoclonal antibody to the rat integrin beta 3 chain, as well as echistatin, a snake venom shown to colocalise with the alpha v chain in osteoclasts, suggesting that the calcium signal is mediated by the alpha v beta 3 form of VNR.(ABSTRACT TRUNCATED AT 250 WORDS)
Shankar
G
G
ICRF Haemopoiesis Research Group, St. Bartholomew's Hospital, London, UK.
Davison
I
I
Helfrich
M H
MH
Mason
W T
WT
Horton
M A
MA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides; D051381:Rats; D016024:Receptors, Cytoadhesin / Q000502:physiology*; D019030:Receptors, Vitronectin; D014757:Viper Venoms / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D014757:Viper Venoms; C057986:echistatin; C047981:arginyl-glycyl-aspartic acid; D002116:Calcitonin; D002118:Calcium