Metabolic activity and gene expression of osteoarthritic chondrocytes in correlation with radiological and histological characteristics.
The aim of this study was to analyze metabolic activity of osteoarthritic chondrocytes in correlation with radiographic, histologic and gene expression data. Six patients with osteoarthritis (OA) of the knee were analyzed clinically and radiographically (Kellgren and Lawrence, K&L). During total knee replacement surgery cartilage samples from the medial and lateral condyles and tibial plateaus were separately harvested. Specimen were analyzed histologically (Mankin Score) and total RNA was extracted. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene beta-actin were measured using quantitative PCR. In order to estimate metabolic activity chondrocytes were cultured in alginate beads and proteoglycan content was measured after 1 week. PG content in cultures was dependent from degradation status of cartilage (medial compartments 20.4 +/- 0.83 ng/ng, lateral compartments 29.9 +/- 3.0 ng/ng P < 0.01). We found a positive correlation of PG content in cultures with Mankin's grading (r = 0.79; P < 0.01) and with K&L scoring (r = 0.57; P = 0.05). There was a considerable variation of expression levels of MMP-3 and AGG. PG metabolism of cultured chondrocytes correlated only with the macroscopic and microscopic degradation status of cartilage. Gene expression showed a high variability and no correlation to PG metabolism indicating a more complex regulation.
Stöve
Johannes
J
Department of Orthopaedic Surgery, Faculty of Clinical Medicine, Mannheim University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. johannes.stoeve@ortho.ma.uni-heidelberg.de
Gremmes
Christina
C
Günther
Klaus Peter
KP
Scharf
Hanns-Peter
HP
Schwarz
Markus
M
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000368:Aged; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000464:Alginates / Q000737:chemistry; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D003470:Culture Media; D004247:DNA / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008863:Microspheres; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013997:Time Factors
D000199:Actins; D053674:Aggrecans; D000464:Alginates; D003470:Culture Media; D011509:Proteoglycans; D012333:RNA, Messenger; D004247:DNA; D019278:Matrix Metalloproteinase 3