Integrin receptor-mediated mobilisation of intranuclear calcium in rat osteoclasts

This is the authors' abstract. We don't add key points for this paper.

Cell-matrix interactions have been shown to play an important role in regulating cell function and behav-iour. In bone, where calcified matrix formation and resorption events are required to be in dynamic equi-librium, 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, αv3). The objective of the study was to investigate changes in intracellular cal-cium, a regulator of osteoclast function, following addition of peptides that bind integrins, in particular the αv3 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 osteo-clasts. 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 3 chain, as well as echistatin, a snake venom shown to colocalise with the αv chain in osteoclasts, suggesting that the calcium signal is mediated by the αv3 form of VNR. In contrast, a uniform increase in [Ca2+]i through-out the osteoclast was observed with the calcium-regu-lating hormone calcitonin, as a consequence of calcium entry from extracellular sources. Addition of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a non-nuclear calcium ATPase inhibitor, resulted in a calcium signal with spatial characteristics distinct from that evoked by calcitonin or RGD-containing peptides. Thus, an increase in intranuclear calcium to the exclusion of a concomitant rise in cytoplasmic [Ca2+]i was restricted to responses induced by RGD-containing peptides. The present findings demonstrate that, in rat osteo-clasts, there is a signalling pathway linked to the inte-grin VNR, which can rapidly modulate the concentration of nuclear [Ca2+]i, which in turn may regulate nuclear calcium-dependent processes.