Sasaki, Takako and Stoop, Reinout and Sakai, Takao and Hess, Andreas and Deutzmann, Rainer and Schloetzer-Schrehardt, Ursula and Chu, Mon-Li and von der Mark, Klaus (2016) Loss of fibulin-4 results in abnormal collagen fibril assembly in bone, caused by impaired lysyl oxidase processing and collagen cross-linking. MATRIX BIOLOGY, 50. pp. 53-66. ISSN 0945-053X, 1569-1802
Full text not available from this repository. (Request a copy)Abstract
The extracellular matrix protein fibulin-4 has been shown to be indispensable for elastic fiber assembly, but there is also evidence from human mutations that it is involved in controlling skeletal development and bone stability. Fibulin-4 mutations were identified in patients suffering from vascular abnormality and/or cutis laxa, and some of these patients exhibited bone fragility, arachnodactyly and joint laxity. In order to elucidate the role of fibulin-4 in bone structure and skeletal development, we analyzed structural changes in skeletal tissues of FbIn(-/-) mice. Immunostaining confirmed that fibulin-4 is highly expressed in cartilage, bone, ligaments and tendons. No morphological abnormalities were found in the skeleton of FbIn(-/-) mice as compared to wild type littermates except forelimb contractures as well as unusually thick collagen fibrils. Furthermore, fibulin-4 deficiency caused enhanced susceptibility of bone collagen for acid extraction, consistent with significantly reduced lysylpyridinoline and hydroxylysylpyridinoline cross-links in bone. In accordance with that, the amount of lysyl oxidase in long bones and calvaria was strongly decreased and proteolytic activation of lysyl oxidase was reduced in fibulin-4 deficient osteoblasts, while addition of recombinant fibulin-4 rescued the activation. The finding suggested that fibulin-4 is important for the proteolytic activation of lysyl oxidase which has a pivotal role in cross-linking of collagen and elastin. (C) 2015 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EXTRACELLULAR-MATRIX PROTEINS; LEUCINE-RICH PROTEOGLYCANS; CUTIS-LAXA; OSTEOGENESIS IMPERFECTA; TISSUE LOCALIZATION; I COLLAGEN; MICE; GENE; DEFICIENCY; FIBRILLOGENESIS; Fibulin-4; Collagen cross-linking; Elastic fiber; Lysyl oxidase |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Rainer Deutzmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2019 12:43 |
| Last Modified: | 11 Mar 2019 12:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2289 |
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