Altered integration of matrilin-3 into cartilage extracellular matrix in the absence of collagen IX.
The matrilins are a family of four noncollagenous oligomeric extracellular matrix proteins with a modular structure. Matrilins can act as adapters which bridge different macromolecular networks. We therefore investigated the effect of collagen IX deficiency on matrilin-3 integration into cartilage tissues. Mice harboring a deleted Col9a1 gene lack synthesis of a functional protein and produce cartilage fibrils completely devoid of collagen IX. Newborn collagen IX knockout mice exhibited significantly decreased matrilin-3 and cartilage oligomeric matrix protein (COMP) signals, particularly in the cartilage primordium of vertebral bodies and ribs. In the absence of collagen IX, a substantial amount of matrilin-3 is released into the medium of cultured chondrocytes instead of being integrated into the cell layer as in wild-type and COMP-deficient cells. Gene expression of matrilin-3 is not affected in the absence of collagen IX, but protein extraction from cartilage is greatly facilitated. Matrilin-3 interacts with collagen IX-containing cartilage fibrils, while fibrils from collagen IX knockout mice lack matrilin-3, and COMP-deficient fibrils exhibit an intermediate integration. In summary, the integration of matrilin-3 into cartilage fibrils occurs both by a direct interaction with collagen IX and indirectly with COMP serving as an adapter. Matrilin-3 can be considered as an interface component, capable of interconnecting macromolecular networks and mediating interactions between cartilage fibrils and the extrafibrillar matrix.
Budde
Bastian
B
Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
Blumbach
Katrin
K
Ylöstalo
Joni
J
Zaucke
Frank
F
Ehlen
Harald W A
HW
Wagener
Raimund
R
Ala-Kokko
Leena
L
Paulsson
Mats
M
Bruckner
Peter
P
Grässel
Susanne
S
D000818:Animals; D000831:Animals, Newborn; D000918:Antibody Specificity; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D024081:Collagen Type IX / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D007106:Immune Sera / Q000276:immunology; D007150:Immunohistochemistry; D064235:Matrilin Proteins; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D011485:Protein Binding; D012995:Solubility
D024081:Collagen Type IX; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007106:Immune Sera; C577540:Matn1 protein, mouse; C577546:Matn3 protein, mouse; D064235:Matrilin Proteins