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  Fkbp10 deletion in osteoblasts leads to qualitative defects in bone

Lietman, C. D., Lim, J., Grafe, I., Chen, Y., Ding, H., Bi, X., et al. (2017). Fkbp10 deletion in osteoblasts leads to qualitative defects in bone. Journal of Bone and Mineral Research, 32(6), 1354-1367. doi:10.1002/jbmr.3108.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-84FB-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-F766-4
Genre: Journal Article

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 Creators:
Lietman, Caressa D., Author
Lim, Joohyun, Author
Grafe, Ingo, Author
Chen, Yuqing, Author
Ding, Hao, Author
Bi, Xiaohong, Author
Ambrose, Catherine G., Author
Fratzl-Zelman, Nadja, Author
Roschger, Paul, Author
Klaushofer, Klaus, Author
Wagermaier, Wolfgang1, Author              
Schmidt, Ingo1, Author              
Fratzl, Peter2, Author              
Rai, Jyoti, Author
Weis, MaryAnn, Author
Eyre, David, Author
Keene, Douglas R., Author
Krakow, Deborah, Author
Lee, Brendan H., Author
Affiliations:
1Wolfgang Wagermaier, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863296              
2Peter Fratzl, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863294              

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Free keywords: osteogenesis imperfecta, matrix mineralization, collagen, osteoblasts, genetic animal models
 Abstract: Osteogenesis Imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65KDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10fl/fl mice (Mus musculus; C57BL/6) using the osteoblast specific Col1a1 2.3kb Cre recombinase. Using µCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy of bone collagen demonstrated a decrease in mature, hydroxylysine-aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral-to-matrix ratio and in crystal size as shown by Raman spectroscopy and small angle x-ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton. This article is protected by copyright. All rights reserved

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 Dates: 2017-06
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.1002/jbmr.3108
PMID: 0522
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Title: Journal of Bone and Mineral Research
Source Genre: Journal
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Publ. Info: Hoboken, New Jersey : Wiley-Blackwell
Pages: - Volume / Issue: 32 (6) Sequence Number: - Start / End Page: 1354 - 1367 Identifier: ISSN: 0884-0431