Hck contributes to bone homeostasis by controlling the recruitment of osteoclast precursors. Issue 9 (6th June 2013)

• Record Type: Journal Article
• Authors: Vérollet, Christel; Gallois, Anne; Dacquin, Romain; Lastrucci, Claire; Pandruvada, Subramanya N. M.; Ortega, Nathalie; Poincloux, Renaud; Behar, Annie; Cougoule, Céline; Lowell, Clifford; Saati, Talal Al; Jurdic, Pierre; Maridonneau‐Parini, Isabelle
• Is Part Of: FASEB journal. Volume 27:Issue 9(2013)
• Page Start: 3608
• Page End: 3618
• Publication Date: 2013-06-06
• Subjects: osteopetrosis -- cell migration -- podosomes -- Src tyrosine kinases; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.13-232736
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract : 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.—Vérollet, C., Gallois, A., Dacquin, R., Lastrucci, C., Pandruvada, S. M. N., Ortega, N., Poincloux, R., Behar, A., Cougoule, C., Lowell, C., Al Saati, T., Jurdic, P., Maridonneau‐Parini, I., Hck contributes to bone homeostasis by controlling the recruitment of osteoclast precursors. FASEB J. 27, 3608–3618 (2013). www.fasebj.org