Human Molecular Genetics Advance Access published online on December 17, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddh034
© 2003 by Oxford University Press
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1 Dept Medicine, McGill University, Royal Victoria Hospital, Montreal QC; Centre for Bone & Periodontal Research, McGill University, Royal Victoria Hospital, Montreal QC; Divisions of Endocrinology, McGill University Health Centre, Royal Victoria Hospital, Montreal QC
* To whom correspondence should be addressed. E-mail: janet.henderson{at}mcgill.ca.
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 labeling of mineralising 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 remodeling, which identifies it as a potential therapeutic target for osteopenic disorders and those associated with defective bone mineralization.
Article
Defective Bone Mineralization and Osteopenia in Young Adult FGFR3-/- Mice
2 Dept Medicine, McGill University, Royal Victoria Hospital, Montreal QC; Centre for Bone & Periodontal Research, McGill University, Royal Victoria Hospital, Montreal QC
3 Dept Medicine, McGill University, Royal Victoria Hospital, Montreal QC; Divisions of Molecular Endocrinology, McGill University Health Centre, Royal Victoria Hospital, Montreal QC
4 Dept Medicine, McGill University, Royal Victoria Hospital, Montreal QC; Centre for Bone & Periodontal Research, McGill University, Royal Victoria Hospital, Montreal QC; Divisions of Calcium Research Laboratory, McGill University Health Centre, Royal Victoria Hospital, Montreal QC
5 Washington University School of Medicine, St Louis MO.
6 Dept Medicine, McGill University, Royal Victoria Hospital, Montreal QC; Centre for Bone & Periodontal Research, Royal Victoria Hospital, Room M11.41, 687 Pine Ave West, Montreal, QC, Canada H3A 1A1; Divisions of Endocrinology, McGill University Health Centre, Royal Victoria Hospital, Montreal QC
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