Journal Article

Defective bone mineralization and osteopenia in young adult FGFR3<sup>−/−</sup> mice

Gladys Valverde-Franco, Hanlong Liu, David Davidson, Sen Chai, Hector Valderrama-Carvajal, David Goltzman, David M. Ornitz and Janet E. Henderson

in Human Molecular Genetics

Volume 13, issue 3, pages 271-284
Published in print February 2004 | ISSN: 0964-6906
Published online December 2003 | e-ISSN: 1460-2083 | DOI:
Defective bone mineralization and osteopenia in young adult FGFR3−/− mice

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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.

Journal Article.  9656 words.  Illustrated.

Subjects: Genetics and Genomics

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