In osteoclasts, Src controls podosome organization and bone degradation, which 
leads to an osteopetrotic phenotype in src(-/-) mice. Since this phenotype was 
even more severe in src(-/-)hck(-/-) mice, we examined the individual 
contribution of Hck in bone homeostasis. Compared to wt mice, hck(-/-) mice 
exhibited an osteopetrotic phenotype characterized by an increased density of 
trabecular bone and decreased bone degradation, although osteoclastogenesis was 
not impaired. Podosome organization and matrix degradation were found to be 
defective in hck(-/-) osteoclast precursors (preosteoclast) but were normal in 
mature hck(-/-) osteoclasts, probably through compensation by Src, which was 
specifically overexpressed in mature osteoclasts. As a consequence of podosome 
defects, the 3-dimensional migration of hck(-/-) preosteoclasts was strongly 
affected in vitro. In vivo, this translated by altered bone homing of 
preosteoclasts in hck(-/-) mice: in metatarsals of 1-wk-old mice, when bone 
formation strongly depends on the recruitment of these cells, reduced numbers of 
osteoclasts and abnormal developing trabecular bone were observed. This 
phenotype was still detectable in adults. In summmary, Hck is one of the very 
few effectors of preosteoclast recruitment described to date and thereby plays a 
critical role in bone remodeling.