title: Intermittent compressive strain may reduce aggrecanase expression in cartilage: a study of chondrocytes in agarose gel.
abstract: We tested the hypothesis that intermittent compressive strain reduces the catabolic actions of interleukin-1 beta on chondrocyte metabolism at the gene expression level. We investigated the effects of intermittent compressive strain on mRNA expression in bovine chondrocytes cultured in agarose gel supplemented with or without interleukin-1 beta. Fifteen percent compressive strain amplitude was applied to agarose-chondrocyte constructs at a frequency of 1 Hz. In the absence of interleukin-1 beta, the strain caused an increase in the mRNA levels of anabolic factors like aggrecan and Type II collagen, compared with the levels of anabolic factors in unstrained constructs. These results suggest that the strain may stimulate matrix production in normal cartilage. Interleukin-1 beta is a powerful catabolic agent; in unstrained agarose-chondrocyte constructs, interleukin-1 beta caused a decrease in the mRNA levels of anabolic factors. However, interleukin-1 beta also caused an increase in the mRNA of catabolic factors like aggrecanase-1, aggrecanase-2, and matrix metalloproteinase-3. In the presence of interleukin-1 beta, the strain reduced the mRNA levels of aggrecanase-1 and aggrecanase-2. These results suggest that intermittent compressive strain may protect cartilage by suppressing the expression of aggrecanase-1 and aggrecanase-2, which are thought to be the major matrix-degrading enzymes responsible for cleaving aggrecan.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawadacho, Shinjuku-ku, Tokyo, Japan. ken-mio@muh.biglobe.ne.jp
authors.forename: Kensuke
authors.initials: K
authors.lastname: Mio
authors.forename: Seiji
authors.initials: S
authors.lastname: Saito
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tomatsu
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
mesh_terms: D000818:Animals; D001483:Base Sequence; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D046508:Culture Techniques; D010450:Endopeptidases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000494:pharmacology*; D023421:Models, Animal; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D013180:Sprains and Strains; D018709:Statistics, Nonparametric
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D010450:Endopeptidases; C083641:aggrecanase