Physical and biological regulation of proteoglycan turnover around chondrocytes in cartilage explants. Implications for tissue degradation and repair.
The development of clinical strategies for cartilage repair and inhibition of matrix degradation may be facilitated by a better understanding of (1) the chondrocyte phenotype in the context of a damaged extracellular matrix, and (2) the roles of biochemical and biomechanical pathways by which matrix metabolism is mediated. Using methods of quantitative autoradiography, we examined the cell-length scale patterns of proteoglycan deposition and turnover in the cell-associated matrices of chondrocytes in adult bovine and calf cartilage explants. Results highlight a rapid turnover in the pericellular matrix, which may indicate spatial organization of PG metabolic pools, and specific biomechanical roles for different matrix regions. Subsequent to injurious compression of calf explants, which resulted in grossly visible tissue cracks and caused a decrease in the number of viable chondrocytes within explants, cell-mediated matrix catabolic processes appeared to increase, resulting in apparently increased rates of proteoglycan turnover around active cells. Furthermore, the influences of cell-stimulatory factors such as IL-1 beta appeared to be delayed in their effects subsequent to injurious compression, suggesting interactions between biomechanical and biochemical pathways of PG degradation. These results may provide a useful reference point in the development of in vitro models for cartilage injury and disease, and hint at possible new approaches in the development of cartilage repair strategies.
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
T M
TM
Quinn
A A
AA
Maung
A J
AJ
Grodzinsky
E B
EB
Hunziker
J D
JD
Sandy
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013997:Time Factors
D006025:Glycosaminoglycans; D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes