Abstract

This is a revised R29 application that seeks to employ the oim/oim mouse as a model for osteogenesis imperfecta (OI) and dentinogenesis imperfecta. Of central interest will be alterations at the mineral-matrix interface.
The first aim i s to assess the validity of the model, specifically focusing on the mineral-matrix interactions. Secondly, the effect of altered collagen structure on mineral formation as opposed to resorption and turnover will be assessed by comparing mineral abnormalities in dentin and bones of the oim/oim mouse. Third, the relative contributions of impaired collagen and impaired mineral to altered bone stiffness will be determined.
The fourth aim will test the effects of a third generation bisphosphonate that is postulated to have on increasing mechanical strength of bones in growing oim/oim mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DE011803-02
Application #
2654455
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1997-02-01
Project End
2002-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Hospital for Special Surgery
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10021

  Publications

Miller, Elizabeth; Delos, Demetris; Baldini, Todd et al. (2007) Abnormal mineral-matrix interactions are a significant contributor to fragility in oim/oim bone. Calcif Tissue Int 81:206-14
Misof, Barbara M; Roschger, Paul; Baldini, Todd et al. (2005) Differential effects of alendronate treatment on bone from growing osteogenesis imperfecta and wild-type mouse. Bone 36:150-8
Camacho, N P; Carroll, P; Raggio, C L (2003) Fourier transform infrared imaging spectroscopy (FT-IRIS) of mineralization in bisphosphonate-treated oim/oim mice. Calcif Tissue Int 72:604-9
McCarthy, Edith A; Raggio, Cathleen L; Hossack, Michael D et al. (2002) Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model. Pediatr Res 52:660-70
Camacho, N P; Raggio, C L; Doty, S B et al. (2001) A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta. Calcif Tissue Int 69:94-101
Camacho, N P; Hou, L; Toledano, T R et al. (1999) The material basis for reduced mechanical properties in oim mice bones. J Bone Miner Res 14:264-72
Camacho, N P; Rinnerthaler, S; Paschalis, E P et al. (1999) Complementary information on bone ultrastructure from scanning small angle X-ray scattering and Fourier-transform infrared microspectroscopy. Bone 25:287-93
Camacho, N P; Dow, D; Toledano, T R et al. (1998) Identification of the oim mutation by dye terminator chemistry combined with automated direct DNA sequencing. J Orthop Res 16:38-42