title: Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial articular hyaline cartilage in osteoarthritis.
abstract: OBJECTIVE
  To measure cartilage pH in patients with osteoarthritis (OA) and to analyze the presence of cathepsin K, the recently discovered acidic endoproteinase, in phenotypically altered chondrocytes.
  
  
  METHODS
  Intraoperative measurements of the pH of clinically normal, fibrillated, superficially fissured, and deeply fissured cartilage surfaces (grades 0-3, respectively) in OA patients undergoing primary hip replacement surgery were performed with the use of a sting electrode sterilized with microbicidic plasma. Fluorescent pH probes were used for in situ assessment of cartilage matrix pH. Cathepsin K was assessed using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry methods.
  
  
  RESULTS
  The pH of grade 0 cartilage surfaces was 7.1 +/- 0.4 (mean +/- SD), compared with 6.2 +/- 0.9 (P < 0.05), 5.7 +/- 1.0 (P < 0.001), and 5.5 +/- 1.0 (P < 0.001) for grades 1-3 cartilage surfaces, respectively. Fluorescent pH probes and acid-dependent autocatalytic conversion of cathepsin K into its active, low molecular weight form in cartilage confirmed these findings. Cathepsin K messenger RNA levels increased in relation to the severity of OA, and the number of cathepsin K-containing chondrocytes increased from a mean +/- SD of 12 +/- 3 in grade 0 cartilage surfaces to 47 +/- 7, 50 +/- 6, and 100 +/- 12 in grades 1-3 cartilage surfaces, respectively (P < 0.001 for all comparisons).
  
  
  CONCLUSIONS
  Acid-activated, but pharmacologically inhibitable, cathepsin K is induced in phenotypically altered chondrocytes in OA. The findings suggest that cathepsin K, rather than neutral matrix metalloproteinases, degrades the superficial gliding surfaces of the articular hyaline cartilage in OA.
authors.affiliation: Helsinki University Hospital and ORTON Research Institute, the Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland. yrjo.konttinen@helsinki.fi
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Jari
authors.initials: J
authors.lastname: Salo
authors.forename: Jan
authors.initials: J
authors.lastname: Lassus
authors.forename: Mikko
authors.initials: M
authors.lastname: Liljeström
authors.forename: Mika
authors.initials: M
authors.lastname: Hukkanen
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
authors.forename: Ismo
authors.initials: I
authors.lastname: Virtanen
authors.forename: Seppo
authors.initials: S
authors.lastname: Santavirta
mesh_terms: D000143:Acids / Q000378:metabolism; D000165:Acridine Orange; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology; D056657:Cathepsin K; D002403:Cathepsins / Q000032:analysis / Q000378:metabolism*; D019902:Chondrocytes / Q000201:enzymology; D004789:Enzyme Activation / Q000502:physiology; D005456:Fluorescent Dyes; D006801:Humans; D006818:Hyalin / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000143:Acids; D005456:Fluorescent Dyes; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D000165:Acridine Orange