Cathepsins B, K, and L are regulated by a defined collagen type II peptide via activation of classical protein kinase C and p38 MAP kinase in articular chondrocytes.
Degradation of the extracellular matrix (ECM) is a prominent feature in osteoarthritis (OA), which is mainly because of the imbalance between anabolic and catabolic processes in chondrocytes resulting in cartilage and bone destruction. Various proteases act in concert to degrade matrix components, e.g. type II collagen, MMPs, ADAMTS, and cathepsins. Protease-generated collagen fragments may foster the destructive process. However, the signaling pathways associated with the action of collagen fragments on chondrocytes have not been clearly defined. The present data demonstrate that the N-terminal telopeptide of collagen type II enhances expression of cathepsins B, K, and L in articular chondrocytes at mRNA, protein, and activity levels, mediated at least in part through extracellular calcium. We also demonstrate that the induction is associated with the activation of protein kinase C and p38 MAP kinase.
Ruettger
Anke
A
Institute of Biochemistry I, Universitätsklinikum, University of Jena, 07743 Jena, Germany.
Schueler
Susann
S
Mollenhauer
Juergen A
JA
Wiederanders
Bernd
B
D002118:Calcium / Q000494:pharmacology; D002401:Cathepsin B / Q000235:genetics* / Q000378:metabolism; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics* / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D003094:Collagen / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007719:Knee Joint; D007720:Knee Prosthesis; D010446:Peptide Fragments / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D010446:Peptide Fragments; D012333:RNA, Messenger; D003094:Collagen; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534130:CTSK protein, human; D056657:Cathepsin K; D002118:Calcium