Abstract
ABSTRACTBone erosion both demands that the osteoclast resorbs bone matrix and moves over the bone surface. It is widely accepted that these two activities alternate, because they are considered mutually exclusive since resorption is believed to involve an immobilizing seal to the bone surface. However, clear real-time observations are still lacking. Herein, we used specific markers and time-lapse to monitor live the spatiotemporal generation of resorption events by osteoclasts cultured on bone slices. In accordance with the current view, we found alternating episodes of resorption and migration resulting in the formation of clusters of round pits. However, very importantly, we also demonstrate that more than half of the osteoclasts moved laterally, displacing their extracellular bone-resorbing compartment over the bone surface without disassembling and reconstructing it, thereby generating long trenches. Compared to pit events, trench events show properties enabling higher aggressiveness: long duration (days), high erosion speed (two times faster) and long-distance erosion (several 100 µm). Simultaneous resorption and migration reflect a unique situation where epithelial/secretory and mesenchymal/migratory characteristics are integrated into just one cell phenotype, and deserves attention in future research.
Highlights
A functional osteoclast (OC) must be able to resorb bone matrix, and to move its resorptive activity over the bone surface (Parfitt, 1993)
Characterization of pit forming OCs by time-lapse Analyses of the time-lapse recordings clearly identified that pit formation occurred exactly in line with the classical resorption cycle model: stationary resorption, which is oriented perpendicular to the bone surface within the area delineated by the sealing zone (SZ)
Note that the OC stands over the pit and that the SZ surrounds it during the whole resorption period, but the SZ seems to be very motile suggesting a continuous reorganization
Summary
A functional osteoclast (OC) must be able to resorb bone matrix, and to move its resorptive activity over the bone surface (Parfitt, 1993). They have been interpreted as a series of contiguous pits according to the logics of the resorption cycle theory (Georgess et al, 2014; Novack and Faccio, 2009; Rumpler et al, 2013; Vives et al, 2011) Their geometry and smooth appearance suggest that they could be interpreted as generated by OCs that persistently resorb laterally, moving across the bone surface (Merrild et al, 2015; Mulari et al, 2003; Nesbitt and Horton, 1997; Soe and Delaisse, 2010; Soe et al, 2013; Stenbeck and Horton, 2000). The kinetics of pit and trench formation were compared
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