Loss of fibulin-4 results in abnormal collagen fibril assembly in bone, caused by impaired lysyl oxidase processing and collagen cross-linking
| Autor: | Ursula Schlötzer-Schrehardt, Takako Sasaki, Takao Sakai, Mon-Li Chu, Klaus von der Mark, Andreas Hess, Rainer Deutzmann, Reinout Stoop |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Elastic fiber assembly Lysyl oxidase Bone and Bones Protein-Lysine 6-Oxidase Extracellular matrix Mice 03 medical and health sciences medicine Animals Humans Tissue Distribution Molecular Biology Cells Cultured Extracellular Matrix Proteins Bone Development 030102 biochemistry & molecular biology biology Chemistry Cartilage Elastin Fibulin Cell biology Collagen type I alpha 1 030104 developmental biology medicine.anatomical_structure Biochemistry Mutation biology.protein Collagen Elastic fiber |
| Zdroj: | Matrix Biology. 50:53-66 |
| ISSN: | 0945-053X |
| DOI: | 10.1016/j.matbio.2015.12.002 |
| Popis: | 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 Fbln4-/- mice. Immunostaining confirmed that fibulin-4 is highly expressed in cartilage, bone, ligaments and tendons. No morphological abnormalities were found in the skeleton of Fbln4-/- 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. © 2015 International Society of Matrix Biology. |
| Databáze: | OpenAIRE |
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