Immunohistochemical demonstration of -(carboxymethyl)lysine protein adducts in normal and osteoarthritic cartilage.
N(epsilon)-(carboxymethyl)lysine (CML) is an advanced glycation end product formed by non-enzymatic glycation and oxidation of proteins. The distribution pattern of CML-modified proteins in normal and osteoarthritic (OA) cartilage was investigated using specific antibodies. In healthy articular cartilage, immunoreactivity for CML was preferably found in the extracellular matrix (ECM) of the superficial layer. In OA samples, CML immunoreactivity was not restricted to the ECM of the superficial layer. Interestingly, OA chondrocytes showed a remarkable cytoplasmic immunoreactivity for CML. With the help of a western blot analysis CML-modified proteins between 68 and 39 kDa could be demonstrated in OA cartilage samples. These results suggest that the accumulation of CML adducts contributes to the matrix damage in osteoarthritis. Therefore, the inhibition of CML accumulation may represent an effective therapeutic strategy to prevent severe OA cartilage injury.
Schwab
Wolfgang
W
Institute of Anatomy, Technical University Dresden, Medical Faculty Carl Gustav Carus, Fiedlerstrasse 42, Germany. Wolfgang.Schwab@mailbox.tu-dresden.de
Friess
Ulrich
U
Hempel
Ute
U
Schulze
Eva
E
Makita
Zenji
Z
Kasper
Michael
M
Simank
Hans-Georg
HG
D015153:Blotting, Western; D002358:Cartilage, Articular / Q000166:cytology* / Q000473:pathology; D016022:Case-Control Studies; D019902:Chondrocytes / Q000737:chemistry / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007719:Knee Joint; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology*; D011506:Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism
D017127:Glycation End Products, Advanced; D011506:Proteins; C048496:N(6)-carboxymethyllysine; D008239:Lysine