Perlecan in late stages of osteoarthritis of the human knee joint.
OBJECTIVE
Disturbances of the proteoglycan metabolism play an essential role in the pathology of osteoarthritis. The extracellular matrix proteoglycan, perlecan, has lately been identified as a cell biological factor in cartilage development and maintenance. We investigated the tissue distribution of perlecan, the relation between the level of the protein and its mRNA and which type of cell, type 1 chondrocytes or elongated secretory type 2 cells, produces perlecan in late stages of osteoarthritis.


METHODS
In 10 patients suffering from late-stage osteoarthritis tissue samples taken from a macroscopically intact area and the area adjacent to the main cartilage defect were investigated. We performed quantitative immunogold histochemistry and in situ hybridization in vivo and determined the level of perlecan mRNA with the help of real-time RT-PCR in native cartilage tissue and in cultured cells.


RESULTS
In vivo, an increased level of perlecan protein was found in the area adjacent to the main defect. A 45% rise in the level of perlecan mRNA secreted by elongated secretory type 2 cells in comparison to type 1 chondrocytes was detected. Type 2 cells also translated the highest levels of perlecan to be deposited mainly in the pericellular matrix, and also in the interterritorial matrix in late stages of osteoarthritis. Also in vitro, type 2 cells showed a 50% higher level of mRNA for perlecan.


CONCLUSIONS
We found evidence that perlecan is involved in the pathogenesis of late stages of osteoarthritis. The levels of perlecan protein and mRNA are up-regulated especially by the elongated secretory type 2 cells in the area adjacent to the main cartilage defect. This might be seen as an attempt on the part of the cartilage tissue to stabilize the extracellular matrix.
Tesche
F
F
Zentrum Anatomie, Abteilung Histologie, Kreuzbergring 36, 37075 Göttingen, Germany.
Miosge
N
N
D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis
D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; C071927:perlecan