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

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschungBegutachtung

AutorInnen

  • Claudia Nicolae
  • Ya-Ping Ko
  • Nicolai Miosge
  • Anja Niehoff
  • Daniel Studer
  • Lukas Enggist
  • Ernst B Hunziker
  • Mats Paulsson
  • Raimund Wagener
  • Atilla Aszodi

Forschungseinrichtungen

Details

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.

OriginalspracheEnglisch
ZeitschriftThe Journal of biological chemistry
Jahrgang282
Heft30
Seiten (von - bis)22163-22175
Seitenumfang13
ISSN0021-9258
DOIs
PublikationsstatusVeröffentlicht - 27.07.2007

ID: 24197

DOI

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