Bone degradation by osteoclasts depends on the formation of a sealing zone, 
composed of an interlinked network of podosomes, which delimits the degradation 
lacuna into which osteoclasts secrete acid and proteolytic enzymes. For 
resorption to occur, the sealing zone must be coherent and stable for extended 
periods of time. Using titanium roughness gradients ranging from 1 to 4.5 µm 
R(a) as substrates for osteoclast adhesion, we show that microtopographic 
obstacles of a length scale well beyond the range of the 'footprint' of an 
individual podosome can slow down sealing-zone expansion. A clear inverse 
correlation was found between ring stability, structural integrity and 
sealing-zone translocation rate. Direct live-cell microscopy indicated that the 
expansion of the sealing zone is locally arrested by steep, three-dimensional 
'ridge-like barriers', running parallel to its perimeter. It was, however, also 
evident that the sealing zone can bypass such obstacles, if pulled by 
neighbouring regions, extending through flanking, obstacle-free areas. We 
propose that sealing-zone dynamics, while being locally regulated by surface 
roughness, are globally integrated via the associated actin cytoskeleton. The 
effect of substrate roughness on osteoclast behaviour is significant in relation 
to osteoclast function under physiological and pathological conditions, and may 
constitute an important consideration in the design of advanced bone 
replacements.