Altered Integration of Matrilin-3 into Cartilage Extracellular Matrix in the Absence of Collagen IX

Abstract

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.

Abnormal bone quality in cartilage oligomeric matrix protein and matrilin 3 double‐deficient mice caused by increased tissue inhibitor of metalloproteinases 3 deposition and delayed aggrecan degradation

“…Even though the total amount of type II collagen seemed to be unchanged, the findings of both the antibody staining and the extractability experiments were markedly changed in the absence of COMP and matrilin 3. We speculate that the fibril structure is altered, since both COMP and matrilin 3 bind to collagens and are known to influence fibrillogenesis and collagen volume density, respectively (4,6,9,10,12). Moreover, consistent with the histologic findings, the physical bone parameters obtained from the peripheral QCT measurements showed alterations in the metaphysis, with an elevation of trabecular bone mineral content and density (Table 1).…”

Identification of differentially expressed genes in the growth plate of broiler chickens with thiram-induced tibial dyschondroplasia

“…Collagen IX stabilizes the individual homogeneously occurring fibrils (Eikenberry & Bruckner, 1999) and is thought to direct the organization at the tissue level of the fibrillar network in cartilage. Interestingly, matrilin-3 can integrate into cartilage fibrils by a direct interaction with collagen IX and, as an adapter, indirectly with the cartilage oligomeric matrix protein (Budde et al, 2005). Therefore, matrilin-3 is considered an interface component, capable of interconnecting macromolecular networks and mediating interactions between cartilage fibrils and the extra fibrillar matrix (Wagener et al, 2005).…”

Increased expression of matrilin‐3 not only in osteoarthritic articular cartilage but also in cartilage‐forming tumors, and down‐regulation of SOX9 via epidermal growth factor domain 1–dependent signaling

“…Taken together, these results clearly show that secreted MATN3 exerts down-regulation of its own expression, both in HCS-2/8 cells and PHCs. Interestingly, in type IX collagen-knockout mice (33), increased solubility of MATN3 was accompanied by decreased MATN3 levels (12). Therefore, the extent of autoregulation of MATN3 expression should be attributed to the size of the soluble pool of secreted MATN3.…”

“…Detailed characterization of MATN3 remains elusive, however. On the one hand, MATN3 is known to interact directly with the pericellular matrix, in which it is believed to play a role in interconnecting macromolecular networks (12)(13)(14)(15). On the other hand, coated MATN3 was demonstrated to promote settling of primary human chondrocytes (PHCs) (16), suggesting that MATN3 interacts physically with cells.…”