1. The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes
- Author
-
K. Honda, Kotaro Tanimoto, Nobuaki Tanaka, Chise Ijuin, Yukio Kato, T. Doi, Kazuo Tanne, and Shigeru Ohno
- Subjects
Cartilage, Articular ,Male ,Histology ,Knee Joint ,Type II collagen ,Cycloheximide ,Matrix metalloproteinase ,Gene Expression Regulation, Enzymologic ,Chondrocyte ,Pathology and Forensic Medicine ,Proinflammatory cytokine ,Weight-Bearing ,chemistry.chemical_compound ,Chondrocytes ,Tensile Strength ,medicine ,Animals ,RNA, Messenger ,Cells, Cultured ,DNA Primers ,Protein Synthesis Inhibitors ,Tissue Inhibitor of Metalloproteinase-1 ,Mechanical load ,biology ,Tumor Necrosis Factor-alpha ,Cartilage ,Cell Biology ,General Medicine ,Extracellular Matrix ,Cell biology ,Phenotype ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,chemistry ,Biochemistry ,Proteoglycan ,biology.protein ,Matrix Metalloproteinase 3 ,Proteoglycans ,Collagen ,Rabbits ,Stress, Mechanical ,Matrix Metalloproteinase 1 ,Interleukin-1 - Abstract
Excessive mechanical load is thought to be responsible for the onset of osteoarthrosis (OA), but the mechanisms of cartilage destruction caused by mechanical loads remain unknown. In this study we applied a high magnitude cyclic tensile load to cultured chondrocytes using a Flexercell strain unit, which produces a change in cell morphology from a polygonal to spindle-like shape, and examined the protein level of cartilage matrixes and the gene expression of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and proinflammatory cytokines such as IL-1beta and TNF-alpha. Toluidine blue staining, type II collagen immunostaining, and an assay of the incorporation of [35S]sulfate into proteoglycans revealed a decrease in the level of cartilage-specific matrixes in chondrocyte cultures subjected to high magnitude cyclic tensile load. PCR-Southern blot analysis showed that the high magnitude cyclic tensile load increased the mRNA level of MMP-1, MMP-3, MMP-9, IL-1beta, TNF-alpha and TIMP-1 in the cultured chondrocytes, while the mRNA level of MMP-2 and TIMP-2 was unchanged. Moreover, the induction of MMP-1, MMP-3 and MMP-9 mRNA expression was observed in the presence of cycloheximide, an inhibitor of protein synthesis. These findings suggest that excessive mechanical load directly changes the metabolism of cartilage by reducing the matrix components and causing a quantitative imbalance between MMPs and TIMPs.
- Published
- 2000