title: Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-deficient mice.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nicolae
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Ko
authors.forename: Nicolai
authors.initials: N
authors.lastname: Miosge
authors.forename: Anja
authors.initials: A
authors.lastname: Niehoff
authors.forename: Daniel
authors.initials: D
authors.lastname: Studer
authors.forename: Lukas
authors.initials: L
authors.lastname: Enggist
authors.forename: Ernst B
authors.initials: EB
authors.lastname: Hunziker
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.forename: Raimund
authors.initials: R
authors.lastname: Wagener
authors.forename: Attila
authors.initials: A
authors.lastname: Aszodi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001846:Bone Development; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000473:pathology*; D003094:Collagen / Q000378:metabolism*; D003433:Crosses, Genetic; D016326:Extracellular Matrix Proteins / Q000172:deficiency*; D006023:Glycoproteins / Q000172:deficiency*; D006720:Homozygote; D064235:Matrilin Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D014057:Tomography, X-Ray Computed
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577539:MATN1 protein, human; C577540:Matn1 protein, mouse; C577546:Matn3 protein, mouse; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D003094:Collagen