Compression loading in vitro regulates proteoglycan synthesis by tendon fibrocartilage

Koob, Thomas J.; Clark, Paul; Hernández, Daniel J.; Thurmond, Frederick A.; Vogel, Kathryn G.

doi:10.1016/0003-9861(92)90127-i

Cited by 80 publications

(45 citation statements)

References 11 publications

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“…CD44 levels and expression of mRNA for HAS3 were increased in strained fibrocartilage cells, highlighting the role for movement-induced stimuli in differential extracellular matrix metabolism during joint development, and showing that strain may differentially regulate HA synthase gene expression [116,117]. Cyclic compression of tendon explants resulted in synthesis and accumulation of large aggregating proteoglycans by resident fibroblasts, indicating an adaptive response in the development of fibrocartilage in locations where tendons are under compression [118,119]. Cyclic stretch of smooth muscle cells upregulated versican and TSG-6 and increased the amount of hyaluronan-versican aggregates [120].…”

Section: Role Of the Pericellular Matrix In Mechanotransduction And Cmentioning

confidence: 92%

Hyaluronan-dependent pericellular matrix☆

Evanko¹,

Tammi²,

Tammi³

et al. 2007

Advanced Drug Delivery Reviews

257

238

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Hyaluronan is a multifunctional glycosaminoglycan that forms the structural basis of the pericellular matrix. Hyaluronan is extruded directly through the plasma membrane by one of three hyaluronan synthases and anchored to the cell surface by the synthase or cell surface receptors such as CD44 or RHAMM. Aggregating proteoglycans and other hyaluronan-binding proteins, contribute to the material and biological properties of the matrix and regulate cell and tissue function. The pericellular matrix plays multiple complex roles in cell adhesion/de-adhesion, and cell shape changes associated with proliferation and locomotion. Time-lapse studies show that pericellular matrix formation facilitates cell detachment and mitotic cell rounding. Hyaluronan crosslinking occurs through various proteins, such as tenascin, TSG-6, inter-alpha-trypsin inhibitor, pentraxin and TSP-1. This creates higher order levels of structured hyaluronan that may regulate inflammation and other biological processes. Microvillous or filopodial membrane protrusions are created by active hyaluronan synthesis, and form the scaffold of hyaluronan coats in certain cells. The importance of the pericellular matrix in cellular mechanotransduction and the response to mechanical strain are also discussed.

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Section: Role Of the Pericellular Matrix In Mechanotransduction And Cmentioning

confidence: 92%

Hyaluronan-dependent pericellular matrix☆

Evanko¹,

Tammi²,

Tammi³

et al. 2007

Advanced Drug Delivery Reviews

257

238

View full text Add to dashboard Cite

show abstract

“…However, there is conflicting evidence whether changes in response to stretch occur at the level of transcription or post transcriptionally (Bradley et al, 2003). Additionally, the synthesis of the cartilage proteoglycan, aggrecan, has been observed to be significantly increased in mechanically compressed tendon fibrocartilage (Koob et al, 1992;Evanko and Vogel, 1993;Vogel, 2004).…”

Section: Introductionmentioning

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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“…Despite the importance of physical therapy in mediating reparative/anabolic effects on diseased or inflamed synovial joints, only limited information is available regarding its mechanism of intracellular actions (15)(16)(17)(18)(19)(20). In vivo, continuous passive motion induces rapid recovery of inflamed joints and augments proteoglycan synthesis (19,20).…”

mentioning

confidence: 99%

Cyclic Tensile Strain Acts as an Antagonist of IL-1β Actions in Chondrocytes

Buckley

Evans

et al. 2000

The Journal of Immunology

103

125

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Inflammatory cytokines play a major role in cartilage destruction in diseases such as osteoarthritis and rheumatoid arthritis. Because physical therapies such as continuous passive motion yield beneficial effects on inflamed joints, we examined the intracellular mechanisms of mechanical strain-mediated actions in chondrocytes. By simulating the effects of continuous passive motion with cyclic tensile strain (CTS) on chondrocytes in vitro, we show that CTS is a potent antagonist of IL-1β actions and acts as both an anti-inflammatory and a reparative signal. Low magnitude CTS suppresses IL-1β-induced mRNA expression of multiple proteins involved in catabolic responses, such as inducible NO synthase, cyclo-oxygenase II, and collagenase. CTS also counteracts cartilage degradation by augmenting mRNA expression for tissue inhibitor of metalloproteases and collagen type II that are inhibited by IL-1β. Additionally, CTS augments the reparative process via hyperinduction of aggrecan mRNA expression and abrogation of IL-1β-induced suppression of proteoglycan synthesis. Nonetheless, the presence of an inflammatory signal is a prerequisite for the observed CTS actions, as exposure of chondrocytes to CTS alone has little effect on these parameters. Functional analysis suggests that CTS-mediated anti-inflammatory actions are not mediated by IL-1R down-regulation. Moreover, as an effective antagonist of IL-1β, the actions of CTS may involve disruption/regulation of signal transduction cascade of IL-1β upstream of mRNA transcription. These observations are the first to show that CTS directly acts as an anti-inflammatory signal on chondrocytes and provide a molecular basis for its actions.

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Compression loading in vitro regulates proteoglycan synthesis by tendon fibrocartilage

Cited by 80 publications

References 11 publications

Hyaluronan-dependent pericellular matrix☆

Hyaluronan-dependent pericellular matrix☆

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

Cyclic Tensile Strain Acts as an Antagonist of IL-1β Actions in Chondrocytes

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