Disease relevance of MATN1

• ETDT evidenced a significant preferential transmission for the 103 bp allele (Chi-square = 5.058, df = 1, P = 0.024) CONCLUSION: The results suggest that the familial idiopathic scoliosis is associated to the MATN1 gene [1].
• Analysis of the association of the matrillin-1 gene (CRTM) with osteoarthritis: comment on the article by Meulenbelt et al [2].
• Autoreactivity against matrilin-1 in a patient with relapsing polychondritis [3].
• RESULTS: Matrilin-1 expression was detected in both patient groups with TMJ ankylosis and arthritis, and the level was remarkably higher in arthritic cartilage [4].
• OBJECTIVE: It has been suggested that genotypic variation in the gene which encodes the matrilin-1 (MATN-1) protein may be involved in the development of hip osteoarthritis (OA) [5].

High impact information on MATN1

• These are the first mutations to be identified in any of the genes encoding the matrilin family of proteins and confirm a role for matrilin-3 in the development and homeostasis of cartilage and bone [6].
• Northern blot, immunohistochemical, and biochemical analyses indicated no compensatory upregulation of any other member of the matrilin family [7].
• Polymorphic dinucleotide repeat in a cartilage matrix protein (CRTM) gene [8].
• In a screen for ligands of matrilin-1, -3, and -4 using an ELISA-style binding assay, COMP was identified as a prominent binding partner for all three, indicating a conservation of the COMP interaction among matrilins [9].
• Interestingly, a distinct heterotrimer consisting of three different chains was formed between matrilin-1, matrilin-2, and matrilin-4 [10].

Biological context of MATN1

• Enhancement of cell adhesion and spreading by a cartilage-specific noncollagenous protein, cartilage matrix protein (CMP/Matrilin-1), via integrin alpha1beta1 [11].
• Matrilin-3 is a recently identified matrix protein of cartilage that shows sequence homology to matrilin-1 (cartilage matrix protein or CMP) [12].
• Primary structure of human matrilin-2, chromosome location of the MATN2 gene and conservation of an AT-AC intron in matrilin genes [13].
• Among these genes, MATN1, which carries a polymorphic microsatellite marker within its sequence, was selected for a linkage analysis [1].
• Attempts to study matrilin function by gene inactivation in mouse have been frustrating and so far not yielded pronounced phenotypes, presumably because of the extensive redundancy within the family allowing compensation by one family member for another [14].

Anatomical context of MATN1

• Materials and Methods: Functional matrilins were decreased by expressing a dominant negative mini-MATN in primary chondrocytes or by using MATN1-null chondrocytes [15].
• Cartilage matrix protein (CMP; also known as matrilin-1), one of the major noncollagenous proteins in most cartilages, binds to aggrecan and type II collagen [11].
• Matrilin-3 and CMP (matrilin-1) were prominent in equimolar amounts in fetal bovine epiphyseal cartilage and absent from adult articular cartilage [16].
• Matrilin-3 forms disulfide-linked oligomers with matrilin-1 in bovine epiphyseal cartilage [16].
• Integrins contribute to the matrilin-mediated cell attachment, but the binding does not lead to formation of focal contacts and reorganisation of the actin cytoskeleton [17].

Other interactions of MATN1

• The abundance of matrilins was also increased by expressing a wildtype MATN1 or MATN3 in chondrocytes [15].
• The matrilin family at present has four members that all share a structure made up of von Willebrand factor A domains, epidermal growth factor-like domains and a coiled coil alpha-helical module [18].
• In the presence of calcium, COMP and matrilin-1 elute together in the gel filtration of cartilage extracts and can be co-immunoprecipitated [9].
• Except for matrilin-4, all matrilins mediate cell attachment, but only for matrilin-1 and -3 the binding is clearly dose dependent and seen already at moderate coating concentrations [17].
• In all trios components, the region of MATN1 gene containing the microsatellite marker was amplified by a polymerase chain reaction [1].

Analytical, diagnostic and therapeutic context of MATN1

• Immunohistochemistry of tissue sections confirmed that both matrilin-1 and matrilin-3 are widely codistributed throughout human skeletal growth cartilage [12].
• Extracts of fetal skeletal cartilage were resolved by SDS-PAGE and candidate matrilin subunits were identified by electrospray mass spectrometry of tryptic peptides [12].
• In addition, nasal vaccination with collagen type II prior to immunization in DA rats significantly decreased the antibody response to matrilin-1 at day 56, but not at earlier time points, indicating a late protective effect on extra-articular cartilage [19].
• The matrilin-1 and -3a genes were mapped to chromosome 19 and 20 respectively by the radiation hybrid method [20].
• The authenticity of the purified hCMP was confirmed by sequence analysis of N-terminal amino acids [21].

References