HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 30, 22163-22175, July 27, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/30/22163    most recent M610994200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nicolae, C. Articles by Aszodi, A. Search for Related Content PubMed PubMed Citation Articles by Nicolae, C. Articles by Aszodi, A. Social Bookmarking                      What's this?

Abnormal Collagen Fibrils in Cartilage of Matrilin-1/Matrilin-3-deficient Mice^*

Claudia Nicolae, Ya-Ping Ko¹, Nicolai Miosge^¶, Anja Niehoff^||, Daniel Studer^**, Lukas Enggist, Ernst B. Hunziker, Mats Paulsson, Raimund Wagener, and Attila Aszodi²

From the Department of Molecular Medicine, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany, the Center for Biochemistry and Center for Molecular Medicine, Medical Faculty, University of Cologne, 50931 Cologne, Germany, the ^¶Department of Prosthodontics, Georg-August-University of Göttingen, 37075 Göttingen, Germany, the ^||Institute of Biomechanics and Orthopaedics, German Sport University of Cologne, 50933 Cologne, Germany, the ^**Department of Anatomy, University of Bern, 3010 Bern, Switzerland, and the ITI Research Institute for Dental and Skeletal Biology, University of Bern, 3010 Bern, Switzerland

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.

Received for publication, November 29, 2006 , and in revised form, March 26, 2007.

^* This study was supported by the Deutsche Forschungsgemeinschaft (AS 150/1-1, 150/1-2; WA 1338/2-3, 1338/2-4, 1338/2-6), the Swiss National Science Foundation (to E. B. H.), and the Max-Planck Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Member of the International Graduate School in Genetics and Functional Genomics at the University of Cologne.

¹ To whom correspondence should be addressed: Dept. of Molecular Medicine, Max Planck Institute for Biochemistry, Am Klopferspitz 18A, 82152 Martinsried, Germany. Tel.: 49-89-8578-2466; Fax: 49-89-8578-2077; E-mail: aszodi{at}biochem.mpg.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Fresquet, T. A. Jowitt, J. Ylostalo, P. Coffey, R. S. Meadows, L. Ala-Kokko, D. J. Thornton, and M. D. Briggs Structural and Functional Characterization of Recombinant Matrilin-3 A-domain and Implications for Human Genetic Bone Diseases J. Biol. Chem., November 30, 2007; 282(48): 34634 - 34643. [Abstract] [Full Text] [PDF]