| First Author | Rajapurohitam V | Year | 2001 |
| Journal | Bone | Volume | 28 |
| Issue | 5 | Pages | 513-23 |
| PubMed ID | 11344051 | Mgi Jnum | J:82886 |
| Mgi Id | MGI:2655907 | Doi | 10.1016/s8756-3282(01)00416-1 |
| Citation | Rajapurohitam V, et al. (2001) The mouse osteopetrotic grey-lethal mutation induces a defect in osteoclast maturation/function. Bone 28(5):513-23 |
| abstractText | The osteopetrotic grey-lethal (gl) mouse mutant displays many similarities to the human malignant autosomal-recessive form of osteopetrosis. In this study, we show that the gl osteopetrotic bone phenotype is characterized by the presence of numerous differentiated multinucleated osteoclasts. A significant increase in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was detected in vivo, suggesting induction of differentiation in the osteoclast lineage as a compensatory mechanism. These gl osteoclast cells demonstrated a defective cytoskeletal reorganization and an underdeveloped ruffled border, a membrane structure essential for active bone resorption. Accordingly, resorption activity of these cells is markedly impaired by four- to tenfold as evaluated with the pit formation assay. This low bone resorption in gl osteoclasts is highly reminiscent of the loss in key enzymes, V-ATPase or cathepsin-K, and in signaling factors, Src or TRAF-6, which were shown not to be significantly altered in gl osteoclasts. Thus, independently of a deficiency in V-ATPase, Src, cathepsin-K, and TRAF-6, the gl mutation results in increased number of osteoclasts, characterized by a disrupted cytoskeleton and an underdeveloped ruffled border. |
