Deletion of the gene encoding c-Cbl alters the ability of osteoclasts to migrate, delaying resorption and ossification of cartilage during the development of long bones

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Abstract

During development of the skeleton, osteoclast (OC) recruitment and migration are required for the vascular invasion of the cartilaginous anlage and the ossification of long bones. c-Cbl lies downstream of the vitronectin receptor and forms a complex with c-Src and Pyk2 in a signaling pathway that is required for normal osteoclast motility. To determine whether the decreased motility we observed in vitro in c-Cbl-/- OCs translated into decreased cell migration in vivo, we analyzed the long bones of c-Cbl -/- mice during development. Initiation of vascularization and replacement of cartilage by bone were delayed in c-Cbl-/- mice, due to decreased osteoclast invasion of the hypertrophic cartilage through the bone collar. Furthermore, c-Cbl-/- mice show a delay in the formation of secondary centers of ossification, a thicker hypertrophic zone of the growth plate, and a prolonged presence of cartilaginous remnants in the spongiosa, confirming a decrease in resorption of the calcified cartilage. Thus, the decrease in motility of c-Cbl-/- osteoclasts observed in vitro results in a decreased ability of osteoclasts to invade and resorb bone and mineralized cartilage in vivo. These results confirm that c-Cbl plays an important role in osteoclast motility and resorbing activity. © 2003 Elsevier Inc. All rights reserved.

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Chiusaroli, R., Sanjay, A., Henriksen, K., Engsig, M. T., Horne, W. C., Gu, H., & Baron, R. (2003). Deletion of the gene encoding c-Cbl alters the ability of osteoclasts to migrate, delaying resorption and ossification of cartilage during the development of long bones. Developmental Biology, 261(2), 537–547. https://doi.org/10.1016/S0012-1606(03)00299-9

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