title: Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs.
abstract: OBJECTIVE
  Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular distribution of PDPN and it's relationships with inflammation was studied in RA treated with biologic disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD).
  
  
  METHODS
  PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of inflammation and cell-typing.
  
  
  RESULTS
  Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA.
  
  
  CONCLUSIONS
  PDPN was markedly increased in the immunologically inflamed RA synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new marker of residual arthritis in local joints for inflammation-associated severe RA.
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, 2-2-2 Iida Nishi, Yamagata 990-9585,. Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Takakubo
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Oki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Naganuma
authors.forename: Kan
authors.initials: K
authors.lastname: Saski
authors.forename: Akiko
authors.initials: A
authors.lastname: Sasaki
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Yang
authors.initials: Y
authors.lastname: Suran
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Konta
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D013583:Synovial Membrane / Q000378:metabolism*; D000098853:Podoplanin
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: Anti-rheumatic drugs; Podoplanin; invasion; podoplanin; rheumatoid arthritis; synovial tissues