Disease relevance of MATN3

• Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia [1].
• CONCLUSIONS: These associations suggest that the MATN3 region also determines susceptibility to spinal disc degeneration and CMC1 osteoarthritis [2].
• Proposed diagnostic criteria for HOA, including digital clubbing and radiographic periostitis, appear 86% sensitive [3].
• The salient clinical features of primary HOA are: a bimodal distribution of disease onset with one peak during the first year of life and the other at age 15, a male predominance (nine to one), uncommon benign joint effusion, and a variety of skin abnormalities resulting from cutaneous hypertrophy or glandular dysfunction [3].
• To study the relationship between osteoarthritis (OA) and osteoporosis (OP), radiographic osteoarthritis lesions of the hands (HOA) were quantified in 300 healthy women, aged 75 years or more, as a subgroup of a cohort originally recruited for a multi-centre study of risk factors for femoral neck fracture [4].

High impact information on MATN3

• 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 [1].
• A genomewide screen of family with autosomal-dominant MED not linked to the EDM1-3 genes provides significant genetic evidence for a MED locus on the short arm of chromosome 2 (2p24-p23), and a search for candidate genes identified MATN3 (ref. 18), encoding matrilin-3, within the critical region [1].
• We have identified two different missense mutations in the exon encoding the von Willebrand factor A (vWFA) domain of matrilin-3 in two unrelated families with MED (EDM5) [1].
• Behavioural functions have been assigned to most of the male-specific sensory neurons by means of cell ablations; for example, the hook sensory neurons HOA and HOB are specifically required for vulva location [5].
• Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3 [6].

Biological context of MATN3

• Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up [7].
• The peak LOD score at this locus coincides with a gene, MATN3, encoding the noncollagenous cartilage extracellular matrix protein, matrilin-3 [6].
• We have isolated a cDNA clone for human matrilin-3 from a cartilage-specific cDNA library [8].
• The polypeptide predicted from the nucleotide sequence of this clone shared 83% identity with matrilin-3 from mouse and 61% with that from chicken [8].
• Matrilin-3 has a similar tissue distribution, while matrilin-2 and -4 occur in a wide variety of extracellular matrices [9].

Anatomical context of MATN3

• Type IX collagen and matrilin-3 (MATN3), also accumulate in the rER cisternae of PSACH chondrocytes, but it is unknown how mutant COMP interacts with these proteins [10].
• Matrilin-3 and CMP (matrilin-1) were prominent in equimolar amounts in fetal bovine epiphyseal cartilage and absent from adult articular cartilage [11].
• Matrilin-3 forms disulfide-linked oligomers with matrilin-1 in bovine epiphyseal cartilage [11].
• In addition to matrilin-3, documented as a component of the bony extracellular matrix, expression of the other three matrilin genes was observed in osteoprogenitor cells and osteoblasts [12].
• These results suggest that in patients with HOA gamma delta TCR+ T cells help to maintain the integrity of the surface epithelium, thereby preserving its protective function [13].

Associations of MATN3 with chemical compounds

• Subsequent screening of the genomic sequence revealed a missense mutation, of a conserved amino acid codon, changing threonine to methionine in the epidermal growth factor-like domain in matrilin-3 [6].
• METHODS: Sagittal and coronal spinopelvic alignments were investigated in 150 patients with HOA and 150 with LBP using radiographs of the whole spine in both anteroposterior and lateral views [14].

Other interactions of MATN3

• A unique matrix organization was identified in which type II procollagen formed a central core surrounded by a protein network of mutant COMP, type IX collagen, and MATN3 [10].
• The mutation analysis resulted in identification of the DTDST mutation in four patients (14%), the COMP mutation in three (10%) and the MATN3 mutation in three (10%) [15].
• MATN3 encodes matrilin-3, a cartilage-specific extracellular matrix protein [16].

Analytical, diagnostic and therapeutic context of MATN3

• Sections with severe osteoarthritic degeneration showed the highest amount of matrilin-3 mRNA, strong signals in in situ hybridization, and prominent protein deposition in the middle and deep cartilage zone [17].
• METHODS: Normal and osteoarthritic cartilage were systematically analysed for matrilin-3 expression, using immunohistochemistry, Western blot analysis, in situ hybridization, and quantitative PCR [17].
• The HOA combined score was positively correlated with increasing age but not with body mass index [4].
• Bone scintigraphy has emerged as the most sensitive test for HOA; in fact, a bone scan may show evidence of periostitis in patients with no other signs, symptoms, or radiographic abnormalities of the disorder [18].
• CONCLUSIONS: Myopic and hyperopic LASIK had different patterns of HOA induction [19].

References