title: Snorc is a novel cartilage specific small membrane proteoglycan expressed in differentiating and articular chondrocytes.
abstract: OBJECTIVE
  Maintenance of chondrocyte phenotype is a major issue in prevention of degeneration and repair of articular cartilage. Although the critical pathways in chondrocyte maturation and homeostasis have been revealed, the in-depth understanding is deficient and novel modifying components and interaction partners are still likely to be discovered. Our focus in this study was to characterize a novel cartilage specific gene that was identified in mouse limb cartilage during embryonic development.
  
  
  METHODS
  Open access bioinformatics tools and databases were used to characterize the gene, predicted protein and orthologs in vertebrate species. Immunohistochemistry and mRNA expression methodology were used to study tissue specific expression. Fracture callus and limb bud micromass culture were utilized to study the effects of BMP-2 during experimental chondrogenesis. Fusion protein with C-terminal HA-tag was expressed in Cos7 cells, and the cell lysate was studied for putative glycosaminoglycan attachment by digestion with chondroitinase ABC and Western blotting.
  
  
  RESULTS
  The predicted molecule is a small, 121 amino acids long type I single-pass transmembrane chondroitin sulfate proteoglycan, that contains ER signal peptide, lumenal/extracellular domain with several threonines/serines prone to O-N-acetylgalactosamine modification, and a cytoplasmic tail with a Yin-Yang site prone to phosphorylation or O-N-acetylglucosamine modification. It is highly conserved in mammals with orthologs in all vertebrate subgroups. Cartilage specific expression was highest in proliferating and prehypertrophic zones during development, and in adult articular cartilage, expression was restricted to the uncalcified zone, including chondrocyte clusters in human osteoarthritic cartilage. Studies with experimental chondrogenesis models demonstrated similar expression profiles with Sox9, Acan and Col2a1 and up-regulation by BMP-2. Based on its cartilage specific expression, the molecule was named Snorc, (Small NOvel Rich in Cartilage).
  
  
  CONCLUSIONS
  A novel cartilage specific molecule was identified which marks the differentiating chondrocytes and adult articular chondrocytes with possible functions associated with development and maintenance of chondrocyte phenotype.
authors.affiliation: Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Heinonen
authors.forename: H
authors.initials: H
authors.lastname: Taipaleenmäki
authors.forename: P
authors.initials: P
authors.lastname: Roering
authors.forename: M
authors.initials: M
authors.lastname: Takatalo
authors.forename: L
authors.initials: L
authors.lastname: Harkness
authors.forename: J
authors.initials: J
authors.lastname: Sandholm
authors.forename: H
authors.initials: H
authors.lastname: Uusitalo-Järvinen
authors.forename: M
authors.initials: M
authors.lastname: Kassem
authors.forename: I
authors.initials: I
authors.lastname: Kiviranta
authors.forename: T
authors.initials: T
authors.lastname: Laitala-Leinonen
authors.forename: A-M
authors.initials: AM
authors.lastname: Säämänen
mesh_terms: D000368:Aged; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002358:Cartilage, Articular / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D006614:Hindlimb / Q000196:embryology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D011508:Chondroitin Sulfate Proteoglycans; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D008565:Membrane Proteins; D011509:Proteoglycans; C569022:Snorc protein, mouse