| First Author | Valverde-Franco G | Year | 2004 |
| Journal | Hum Mol Genet | Volume | 13 |
| Issue | 3 | Pages | 271-84 |
| PubMed ID | 14681299 | Mgi Jnum | J:90055 |
| Mgi Id | MGI:3042353 | Doi | 10.1093/hmg/ddh034 |
| Citation | Valverde-Franco G, et al. (2004) Defective bone mineralization and osteopenia in young adult FGFR3-/- mice. Hum Mol Genet 13(3):271-84 |
| abstractText | Mutations that cause constitutive activation of fibroblast growth factor receptor 3 (FGFR3) result in skeletal disorders that are characterized by short-limbed dwarfism and premature closure of cranial sutures. In previous work, it was shown that congenital deficiency of FGFR3 led to skeletal overgrowth. Using a combination of imaging, classic histology and molecular cell biology we now show that young adult FGFR3(-/-) mice are osteopenic due to reduced cortical bone thickness and defective trabecular bone mineralization. The reduction in mineralized bone and lack of trabecular connectivity observed by micro-computed tomography were confirmed in histological and histomorphometric analyses, which revealed a significant decrease in calcein labelling of mineralizing surfaces and a significant increase in osteoid in the long bones of 4-month-old FGFR3(-/-) mice. These alterations were associated with increased staining for recognized markers of differentiated osteoblasts and increased numbers of tartrate-resistant acid phsophatase postitive osteoclasts. Primary cultures of adherent bone marrow-derived cells from FGFR3(-/-) mice expressed markers of differentiated osteoblasts but developed fewer mineralized nodules than FGFR3(+/+) cultures of the same age. Our observations reveal a role for FGFR3 in post-natal bone growth and remodelling, which identifies it as a potential therapeutic target for osteopenic disorders and those associated with defective bone mineralization. |
