Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial articular hyaline cartilage in osteoarthritis.
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.
Konttinen
Yrjö T
YT
Helsinki University Hospital and ORTON Research Institute, the Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland. yrjo.konttinen@helsinki.fi
Mandelin
Jami
J
Li
Tian-Fang
TF
Salo
Jari
J
Lassus
Jan
J
Liljeström
Mikko
M
Hukkanen
Mika
M
Takagi
Michiaki
M
Virtanen
Ismo
I
Santavirta
Seppo
S
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
D000143:Acids; D005456:Fluorescent Dyes; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D000165:Acridine Orange