title: Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis.
abstract: OBJECTIVE
  To investigate the effect of arthritis development and progression on the integrity and function of lubricin and the relationship of lubricin to cartilage damage in a rat antigen-induced arthritis model.
  
  
  METHODS
  Arthritis was induced in the right knee joints, using methylated bovine serum albumin and Freund's complete adjuvant. Whole joint friction measurements were performed ex vivo with a modified Stanton pendulum configuration, and coefficients of friction (mu) were determined. Levels of messenger RNA (mRNA) for lubricin, cathepsin B, and interleukin-1beta (IL-1beta) in synovial tissue from control and affected joints were determined by quantitative polymerase chain reaction. Lubricin staining in cartilage was performed using a lubricin-specific monoclonal antibody.
  
  
  RESULTS
  The mu values in excised right joints following arthritis induction were significantly (P < 0.001) higher than those in excised left joints. Lubricin mRNA expression levels in synovial tissue on days 4 and 7 after arthritis induction were significantly (P < 0.001) lower in the right joints compared with the left joints, whereas levels of cathepsin B and IL-1beta mRNA expression on days 4, 7, and 14 were significantly (P < 0.001) higher in the right joints than the left joints. Lubricin staining was diminished in cartilage from the right joints compared with the left joints.
  
  
  CONCLUSIONS
  Elevated coefficients of friction in arthritic joints occur concurrently with enhanced proteolytic degradation by up-regulated cathepsin B and other proteases, as well as decreased lubricin synthesis by synovial fibroblasts and superficial zone chondrocytes. Loss of joint lubrication is an early event in inflammatory arthropathy. Restoring chondroprotection and preventing potential wear-induced cartilage degradation may require lubricin supplementation in synovial fluid.
authors.affiliation: Rhode Island Hospital, Providence, RI 02881, USA.
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Elsaid
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Jay
authors.forename: Clinton O
authors.initials: CO
authors.lastname: Chichester
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D017276:Friction; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007596:Joints / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008153:Lubrication; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D000099158:Proteoglycan 4
chemical_list: D000276:Adjuvants, Immunologic; D002401:Cathepsin B; D006023:Glycoproteins; D053583:Interleukin-1beta; D012333:RNA, Messenger; D000099158:Proteoglycan 4