title: Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis.
abstract: BACKGROUND
  Multinucleated giant cells have been noticed in diverse arthritic conditions since their first description in rheumatoid synovium. However, their role in the pathogenesis of osteoarthritis (OA) or rheumatoid arthritis (RA) still remains broadly unknown. We aimed to study the presence and characteristics of multinucleated giant cells (MGC) both in synovium and in subchondral bone tissues of patients with OA or RA.
  
  
  METHODS
  Knee synovial and subchondral bone samples were from age-matched patients undergoing total joint replacement for OA or RA, or non-arthritic post mortem (PM) controls. OA synovium was stratified by histological inflammation grade using index tissue sections. Synovitis was assessed by Krenn score. Histological studies employed specific antibodies against macrophage markers or cathepsin K, or TRAP enzymatic assay.
  
  
  RESULTS
  Inflamed OA and RA synovia displayed more multinucleated giant cells than did non-inflamed OA and PM synovia. There was a significant association between MGC numbers and synovitis severity. A TRAP negative/cathepsin K negative Langhans-like subtype was predominant in OA, whereas both Langhans-like and TRAP-positive/cathepsin K-negative foreign-body-like subtypes were most commonly detected in RA. Plasma-like and foam-like subtypes also were observed in OA and RA synovia, and the latter was found surrounding adipocytes. TRAP positive/cathepsin K positive osteoclasts were only identified adjacent to subchondral bone surfaces. TRAP positive osteoclasts were significantly increased in subchondral bone in OA and RA compared to PM controls.
  
  
  CONCLUSIONS
  Multinucleated giant cells are associated with synovitis severity, and subchondral osteoclast numbers are increased in OA, as well as in RA. Further research targeting multinucleated giant cells is warranted to elucidate their contributions to the symptoms and joint damage associated with arthritis.
authors: Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Avda Reyes Católicos, 2, Madrid, 28040, Spain. ivan.prieto@fjd.es.
authors: Iván
authors: I
authors: Prieto-Potin
authors: Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Avda Reyes Católicos, 2, Madrid, 28040, Spain. rlargo@fjd.es.
authors: Raquel
authors: R
authors: Largo
authors: Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Avda Reyes Católicos, 2, Madrid, 28040, Spain. jaromanblas@gmail.com.
authors: Jorge A
authors: JA
authors: Roman-Blas
authors: Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Avda Reyes Católicos, 2, Madrid, 28040, Spain. gherrero@fjd.es.
authors: Gabriel
authors: G
authors: Herrero-Beaumont
authors: Arthritis Research UK Pain Centre, Department of Academic Rheumatology, University of Nottingham, City Hospital, Clinical Sciences Building, Hucknall Road, Nottingham, NG5 1PB, UK. david.walsh@nottingham.ac.uk.
authors: David A
authors: DA
authors: Walsh
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology*; D015415:Biomarkers; D002118:Calcium / Q000627:therapeutic use; D056657:Cathepsin K / Q000032:analysis; D003430:Cross-Sectional Studies; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D015726:Giant Cells / Q000737:chemistry / Q000648:ultrastructure*; D015744:Giant Cells, Langhans / Q000737:chemistry / Q000648:ultrastructure; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D007719:Knee Joint / Q000473:pathology*; D008264:Macrophages / Q000737:chemistry / Q000145:classification / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000473:pathology*; D010010:Osteoclasts / Q000737:chemistry / Q000648:ultrastructure; D012107:Research Design; D016037:Single-Blind Method; D013583:Synovial Membrane / Q000473:pathology*; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000473:pathology*; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D015415:Biomarkers; D004164:Diphosphonates; D005938:Glucocorticoids; D007527:Isoenzymes; D014807:Vitamin D; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C534130:CTSK protein, human; D056657:Cathepsin K; D002118:Calcium