Cyclic Mechanical Stress Induces Extracellular Matrix Degradation in Cultured Chondrocytes via Gene Expression of Matrix Metalloproteinases and Interleukin-1

Fujisawa, Takuo; Hattori, Takako; Takahashi, Koichi; Kuboki, Takuo; Yamashita, Atsushi; Takigawa, Masaharu

doi:10.1093/oxfordjournals.jbchem.a022376

Cited by 152 publications

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“…We found that mechanical strain loaded on the chondrocytes clearly enhanced ROS production. It is worth noting that Fujisawa et al reported enhanced production of interleukin-1 (IL-1) with cyclic tensile stretch using chondrocytes (15). It is well accepted that chondrocytes possess an NADPH oxidase and produce ROS (16).…”

Section: Discussionmentioning

confidence: 99%

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: Involvement of reactive oxygen species

Yamazaki¹,

Fukuda²,

Matsukawa³

et al. 2003

Arthritis & Rheumatism

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Objective. We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (HA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result of mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action.Methods. ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument. Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively.Results. ROS depolymerized HA molecules. Cyclic tensile stretch depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress.Conclusion. ROS play an important role in mechanical stress-induced HA depolymerization.

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Section: Discussionmentioning

confidence: 99%

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: Involvement of reactive oxygen species

Yamazaki¹,

Fukuda²,

Matsukawa³

et al. 2003

Arthritis & Rheumatism

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“…Moreover, biomechanical forces such as tension, compression and shear have been shown to modulate the activity of MMP-2 in chondrocytes (Fujisawa et al, 1999), ligaments (Zhou et al, 2005), muscle (O'Callaghan and Williams, 2000;Auluck et al, 2005) and in the cardiovascular system (Milkiewicz et al, 2005;Rastogi et al, 2005).…”

Section: Effect Of Equibiaxial Stretch On Mmp-2 Activitymentioning

confidence: 99%

Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts

Shelton

Rada

2007

Experimental Eye Research

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In order to understand the effect of mechanical strain on scleral extracellular matrix remodeling, human scleral fibroblasts were subjected to equibiaxial stretch in vitro and the expression of proteoglycans, metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-2 (TIMP-2) were evaluated.Isolated human scleral fibroblasts were seeded onto flexible bottom culture plates, and subjected to a cyclic stretch regimen of 15% equibiaxial stretch for 45 seconds followed by 15 seconds of rest for 6 -48 hours in the presence of 35 SO 4 . Newly synthesized proteoglycans were measured in the medium by CPC precipitation of radiolabelled glycosaminoglycans. MMP-2 activity and expression levels were measured in the medium by, Western blot, gel zymography and real-time PCR. Steady state levels of TIMP-2 mRNA and membrane-type MMP, MT1-MMP (MMP-14) mRNA were measured in the cell layer using real-time PCR.The predominant gelatinolytic enzyme secreted by scleral fibroblasts was the pro-enzyme form of MMP-2 (ProMMP-2). Mechanical stretch resulted in a significant increase of ProMMP-2 after 12 and 48 hours (+76.28%, p < 0.05; +19.56%, p < 0.01, respectively). Mechanical stretch significantly increased the production of the active form of MMP-2 (ActiveMMP-2) after 48 hours (+59.72%, p < 0.05) and decreased levels of TIMP-2 mRNA (−22%, p < 0.05). The rate of scleral proteoglycan synthesis and the steady state levels of MMP-2 and MMP-14 mRNA were not significantly affected by mechanical stretch.These results suggest that mechanical strain stimulates the activation of MMP-2 by scleral fibroblasts, possibly through increased levels of ProMMP-2 and reduced levels of TIMP-2. Increased levels of ActiveMMP-2 in the sclera would be expected to contribute to scleral extracellular matrix degradation, scleral thinning and possible ocular ectasia.

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“…The results of our study raise the question of whether cartilage of the hip joints may be even more sensitive to IL-1␤ stimulation. It has also been reported that excessive and continuous mechanical stress induces production of IL-1␤ by chondrocytes (34). Hip joints are subjected to especially high (multiplied) load stresses during normal walking, due to the femoral neck/lever arm effect counterbalanced by the force exerted by the abductor muscles (35).…”

Section: Il-1 Gene Cluster Polymorphisms and Pathogenesis Of Hip Oamentioning

confidence: 99%

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

Meulenbelt

Seymour

Nieuwland

et al. 2004

Arthritis & Rheumatism

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Objective. To study the role of the interleukin-1␤ gene (IL1B) and the IL-1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine.Methods. The study population consisted of a random sample of 886 subjects (ages 55-65 years) from a population-based cohort (the Rotterdam study). Two polymorphisms within IL1B (3953C>T and ؊511C>T) and one within IL1RN (the variable-number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA. Haplotyping and simultaneous logistic regression analysis were performed to investigate whether the associations observed were independent.Results. Associations with a predisposition for hip ROA were observed for heterozygous and homozygous carriers of the rare IL1B allele ؊511T (crude odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.0-3.4 and OR 2.9, 95% CI 1.4-6.3, respectively) and of the IL1RN VNTR allele 2 (crude OR 2.0, 95% CI 1.1-3.4 and OR 3.3, 95% CI 1.4-7.8, respectively). An additive effect was observed for carriers of risk alleles of both polymorphisms, with a significant linear-by-linear association (P ‫؍‬ 0.00022). Conclusion.Our findings suggest that the IL-1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.Osteoarthritis (OA) is a joint disease characterized by degeneration of articular cartilage and remodeling of the subchondral bone with sclerosis. It has been demonstrated that genetic factors also play an important role in late-onset OA. Familial aggregation of OA (especially hand, knee, and hip OA) was observed in population-based studies (1-4). Candidate genes that may exert this genetic influence have been investigated by means of population-based association studies and genetic linkage studies in OA families. A large number of association studies using various definitions of OA have been performed, mainly investigating genes encoding structural proteins of the extracellular matrix of cartilage (e.g., COL2A1, CRTM, and AGN) or genes playing a role in the regulation of bone density and mass (e.g., VDR, IGF1, and ER), and have shown both positive and negative results for each of the genes (for review, see ref. 5). These differences in study results may indicate either false-positive or false-negative results, could be the result of differences in the OA phenotype investigated, or could be attributable to different linkage disequilibrium (LD) between the associated polymorphism and the causal mutation in various populations. Moreover, it is becoming increasingly clear that the genetic risk factors for OA at different joint sites may be distinct (6).Several groups of investigators have performed genome-wide screens of sibling pairs or nuclear families with OA and reported multiple chromosome areas (e.g., 2p24, 3p12, 4q32, 11q12, 4q27, Xp11.3, and 7p22) that show positive linkage to specific OA phenotypes, such as radiographic OA (ROA) in the distal interphalangeal (DIP) joints, s...

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Cyclic Mechanical Stress Induces Extracellular Matrix Degradation in Cultured Chondrocytes via Gene Expression of Matrix Metalloproteinases and Interleukin-1

Cited by 152 publications

References 0 publications

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: Involvement of reactive oxygen species

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: Involvement of reactive oxygen species

Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

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