| First Author | Kawamata A | Year | 2011 |
| Journal | J Cell Physiol | Volume | 226 |
| Issue | 12 | Pages | 3087-93 |
| PubMed ID | 21732353 | Mgi Jnum | J:309065 |
| Mgi Id | MGI:6756068 | Doi | 10.1002/jcp.22909 |
| Citation | Kawamata A, et al. (2011) Dok-1 and Dok-2 deficiency induces osteopenia via activation of osteoclasts. J Cell Physiol 226(12):3087-93 |
| abstractText | Osteoporosis causes fractures that lead to reduction in the quality of life and it is one of the most prevalent diseases as it affects approximately 10% of the population. One of the important features of osteoporosis is osteopenia. However, its etiology is not fully elucidated. Dok-1 and Dok-2 are adaptor proteins acting downstream of protein tyrosine kinases that are mainly expressed in the cells of hematopoietic lineage. Although these proteins negatively regulate immune system, their roles in bone metabolism are not understood. Here, we analyzed the effects of Dok-1 and Dok-2 double-deficiency on bone. Dok-1/2 deficiency reduced the levels of trabecular and cortical bone mass compared to wildtype. In addition, Dok-1/2 deficiency increased periosteal perimeters and endosteal perimeters of the mid shaft of long bones. Histomorphometric analysis of the bone parameters indicated that Dok-1/2 deficiency did not significantly alter the levels of bone formation parameters including mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR). In contrast, Dok-1/2 deficiency enhanced the levels of bone resorption parameters including osteoclast number (N.Oc/BS) and osteoclast surface (Oc.S/BS). Analyses of individual osteoclastic activity indicated that Dok-1/2 deficiency enhanced pit formation. Systemically, Dok-1/2 deficiency increased the levels of urinary deoxypyridinoline (Dpyr). Search for the target point of the Dok-1/2 deficiency effects on osteoclasts identified that the mutation enhanced sensitivity of osteoclast precursors to macrophage colony-stimulating factor. These data revealed that Dok-1 and Dok-2 deficiency induces osteopenia by activation of osteoclasts. |
