Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-deficient mice

Nicolae, Claudia; Ko, Ya-Ping; Miosge, Nicolai; Niehoff, Anja; Studer, Daniel; Enggist, Lukas; Hunziker, Ernst B; Paulsson, Mats; Wagener, Raimund; Aszodi, Attila (2007). Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-deficient mice. Journal of biological chemistry, 282(30), pp. 22163-75. Bethesda, Md.: American Society for Biochemistry and Molecular Biology 10.1074/jbc.M610994200

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Matrilins are oligomeric extracellular matrix adaptor proteins mediating interactions between collagen fibrils and other matrix constituents. All four matrilins are expressed in cartilage and mutations in the human gene encoding matrilin-3 (MATN3) are associated with different forms of chondrodysplasia. Surprisingly, however, Matn3-null as well as Matn1- and Matn2-null mice do not show an overt skeletal phenotype, suggesting a dominant negative pathomechanism for the human disorders and redundancy/compensation among the family members in the knock-out situation. Here, we show that mice lacking both matrilin-1 and matrilin-3 develop an apparently normal skeleton, but exhibit biochemical and ultrastructural abnormalities of the knee joint cartilage. At the protein level, an altered SDS-PAGE band pattern and a clear up-regulation of the homotrimeric form of matrilin-4 were evident in newborn Matn1/Matn3 and Matn1 knock-out mice, but not in Matn3-null mice. The ultrastructure of the cartilage matrix after conventional chemical fixation was grossly normal; however, electron microscopy of high pressure frozen and freeze-substituted samples, revealed two consistent observations: 1) moderately increased collagen fibril diameters throughout the epiphysis and the growth plate in both single and double mutants; and 2) increased collagen volume density in Matn1(-/-)/Matn3(-/-) and Matn3(-/-) mice. Taken together, our results demonstrate that matrilin-1 and matrilin-3 modulate collagen fibrillogenesis in cartilage and provide evidence that biochemical compensation might exist between matrilins.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie

UniBE Contributor:

Studer, Daniel Franz and Hunziker, Ernst Bruno

ISSN:

0021-9258

ISBN:

17502381

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:55

Last Modified:

04 May 2014 23:16

Publisher DOI:

10.1074/jbc.M610994200

PubMed ID:

17502381

Web of Science ID:

000248196800062

URI:

https://boris.unibe.ch/id/eprint/23550 (FactScience: 42280)

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