title: Cartilage in facet joints of patients with ankylosing spondylitis (AS) shows signs of cartilage degeneration rather than chondrocyte hypertrophy: implications for joint remodeling in AS.
abstract: BACKGROUND
  In ankylosing spondylitis (AS), joint remodeling leading to joint ankylosis involves cartilage fusion. Here, we analyzed whether chondrocyte hypertrophy is involved in cartilage fusion and subsequent joint remodeling in AS.
  
  
  METHODS
  We assessed the expression of chondrocyte hypertrophy markers runt-related transcription factor 2 (Runx2), type X collagen (COL10), matrix metalloproteinase 13 (MMP13), osteocalcin and beta-catenin and the expression of positive bone morphogenic proteins (BMPs) and negative regulators (dickkopf-1 (DKK-1)), sclerostin, (wingless inhibitory factor 1 (wif-1)) of chondrocyte hypertrophy in the cartilage of facet joints from patients with AS or osteoarthritis (OA) and from autopsy controls (CO) by immunohistochemistry. Sex determining region Y (SRY)-box 9 (Sox9) and type II collagen (COL2) expression was assessed as indicators of chondrocyte integrity and function.
  
  
  RESULTS
  The percentage of hypertrophic chondrocytes expressing Runx2, COL10, MMP13, osteocalcin or beta-catenin was significantly increased in OA but not in AS joints compared to CO joints. Frequencies of sclerostin-positive and DKK-1-positive chondrocytes were similar in AS and CO. In contrast, wif-1- but also BMP-2- and BMP-7-expressing and Sox9-expressing chondrocytes were drastically reduced in AS joints compared to CO as well as OA joints whereas the percentage of COL2-expressing chondrocytes was significantly higher in AS joints compared to CO joints.
  
  
  CONCLUSIONS
  We found no evidence for chondrocyte hypertrophy within hyaline cartilage of AS joints even in the presence of reduced expression of the wnt inhibitor wif-1 suggesting that chondrocyte hypertrophy is not a predominant pathway involved in joint fusion and remodeling in AS. In contrast, the reduced expression of Sox9, BMP-2 and BMP-7 concomitantly with induced COL2 expression rather point to disturbed cartilage homeostasis promoting cartilage degeneration in AS.
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, 12203, Berlin, Germany. janine.bleil@charite.de.
authors.forename: Janine
authors.initials: J
authors.lastname: Bleil
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, 12203, Berlin, Germany. joachim.sieper@charite.de.|Deutsches Rheuma-Forschungszentrum, Charitéplatz 1, 10117, Berlin, Germany. joachim.sieper@charite.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.affiliation: Deutsches Rheuma-Forschungszentrum, Charitéplatz 1, 10117, Berlin, Germany. rene-philipp.maier@charite.de.
authors.forename: Rene
authors.initials: R
authors.lastname: Maier
authors.affiliation: Charité Universitätsmedizin Berlin, Institut für Pathologie, Charitéplatz 1, 10117, Berlin, Germany. uwe.schlichting@charite.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlichting
authors.affiliation: Werner-Wicker-Klinik, Im Kreuzfeld 4, 34537, Bad Wildungen, Germany. hempfing@werner-wicker-klinik.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Hempfing
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, 12203, Berlin, Germany. uta.syrbe@charite.de.|Deutsches Rheuma-Forschungszentrum, Charitéplatz 1, 10117, Berlin, Germany. uta.syrbe@charite.de.
authors.forename: Uta
authors.initials: U
authors.lastname: Syrbe
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, 12203, Berlin, Germany. heiner.appel@charite.de.
authors.forename: Heiner
authors.initials: H
authors.lastname: Appel
mesh_terms: D000328:Adult; D000368:Aged; D002357:Cartilage Diseases / Q000175:diagnosis* / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000175:diagnosis* / Q000378:metabolism; D021801:Zygapophyseal Joint / Q000378:metabolism / Q000473:pathology*