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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.Hyaline cartilage is a unique tissue, which contains relatively few cells (chondrocytes) embedded in an abundant extracellular matrix (ECM).3 The cartilage ECM assembles from collagens, proteoglycans, and non-collagenous glycoproteins that interact with each other and are organized into molecular networks. Heterotypic collagen fibrils, containing collagens II, IX, and XI, and the proteoglycan aggrecan, which forms large aggregates with hyaluronic acid, constitute the major structural components of the matrix providing tissue tensile strength and resistance against compressive forces, respectively. In addition to fibril forming collagens, articular cartilage contains beaded microfilament-forming collagen VI, while hypertrophic chondrocytes secrete collagen X. Other cartilage-specific ECM proteins play a role in matrix assembly by regulating collagen fibrillogenesis via binding to the surface of collagen fibers or by mediating interactions between the matrix and the chondrocytes.The matrilin family of ECM proteins is comprised of four structurally related members (1, 2). They contain one (matrilin-3) or two von Willebrand factor A (VWA) domain(s) (matrilin-1, -2, and -4), at least one epidermal growth factor (EGF)-like motif, and a C-terminal coiled-coil domain, which allows the formation of homo-and hetero-oligomers of variable stoichiometry. In mouse, matrilin-1 and matrilin-3 are expressed almost exclusively in cartilaginous tissues (3, ...

The incorporation of a protein into a biomimetically prepared calcium-phosphate coating increases its resistance to the shear forces that are generated during implant insertion. In a clinical setting, the incorporated protein would be an osteogenic agent, whose osteoinductive potential would not be compromised by the shearing off of coating material, and the osteoconductivity of an exposed implant surface would not be less than that of a coated one.

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