Cyclic tensile stress exerts antiinflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase.

Continuous passive motion manifests therapeutic effects on inflamed articular joints by an as-yet-unknown mechanism. Here, we show that application of cyclic tensile stress (CTS) in vitro abrogates the catabolic effects of IL-1beta on chondrocytes. The effects of CTS are mediated by down-regulation of IL-1beta-dependent inducible NO production, and are directly attributed to the inhibition of inducible NO synthase (iNOS) mRNA expression and protein synthesis. The inhibition of iNOS induction by CTS is paralleled by abrogation of IL-1beta-induced down-regulation of proteoglycan synthesis. Furthermore, CTS inhibits iNOS expression and up-regulates proteoglycan synthesis at concentrations of IL-1beta frequently observed in inflamed arthritic joints, suggesting that the actions of CTS may be clinically relevant in suppressing the sustained effects of pathological levels of IL-1beta in vivo. These results are the first to demonstrate that mechanisms of the intracellular actions of CTS in IL-1beta-activated chondrocytes are mediated through inhibition of a key molecule in the signal transduction pathway that leads to iNOS expression.

• Publication year

  1999

• Venue

  Journal of Immunology

• Publication date

  1999-08-15

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.4049/jimmunol.163.4.2187PMID 10438960PMCID PMC4967410
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Factors related to degradation of articular cartilage in osteoarthritis: a review.

  1998cited by this paper
• Nitric oxide and inflammatory joint diseases.

  1998cited by this paper
• Nitric oxide in arthritis.

  1998cited by this paper
• Differences in nitric oxide production by superficial and deep human articular chondrocytes: implications for proteoglycan turnover in inflammatory joint diseases.

  1998cited by this paper
• Quantitative measurement of mRNA expression by competitive RT-PCR.

  1998influential reference
• Chondrocytes in culture produce a mechanically functional tissue

  1998cited by this paper
• Pregnancy induces complex changes in the the pattern of mRNA expression in knee ligaments of the adolescent rabbit.

  1998cited by this paper
• Dynamic mechanical compression influences nitric oxide production by articular chondrocytes seeded in agarose.

  1998cited by this paper
• Chemiluminescent detection of protein molecular weight markers in western blot techniques.

  1997cited by this paper
• Nitric oxide and G proteins mediate the response of bovine articular chondrocytes to fluid‐induced shear

  1997cited by this paper
• Cyclic tensile stretch on bovine articular chondrocytes inhibits protein kinase C activity.

  1997cited by this paper
• Nitric oxide and proteoglycan turnover in rabbit articular cartilage

  1997cited by this paper
• Nitric oxide production by superficial and deep articular chondrocytes.

  1997influential reference
• Composition of cartilagenous tissue with mineralized and non-mineralized zones formed in vitro.

  1997cited by this paper
• The superficial layer of human articular cartilage is more susceptible to interleukin-1-induced damage than the deeper layers.

  1996influential reference
• The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures.

  1996cited by this paper
• Transmission of rapidly applied loads through articular cartilage. Part 1: Uncracked cartilage.

  1996cited by this paper
• Biologic basis for interleukin-1 in disease.

  1996cited by this paper
• Immunohistochemical localization of nitric oxide synthases.

  1996cited by this paper
• Nitric oxide and cartilage metabolism.

  1996cited by this paper
• Protein-tyrosine phosphatase inhibitors block tumor necrosis factor-dependent activation of the nuclear transcription factor NF-kappa B.

  1995cited by this paper
• Differentiation-dependent effects of IL-1 and TGF-beta on human articular chondrocyte proliferation are related to inducible nitric oxide synthase expression.

  1995cited by this paper
• Protein-tyrosine Phosphatase Inhibitors Block Tumor Necrosis Factor-dependent Activation of the Nuclear Transcription Factor NF-B (*)

  1995cited by this paper
• Nitric oxide activates metalloprotease enzymes in articular cartilage.

  1995cited by this paper
• Cytokine regulation of chondrocyte functions.

  1995influential reference
• Effects of continuous passive motion and immobilization on synovitis and cartilage degradation in antigen induced arthritis.

  1995cited by this paper
• Biologic resurfacing of a major joint defect with cryopreserved allogeneic periosteum under the influence of continuous passive motion in a rabbit model.

  1994cited by this paper
• The physiologic basis of continuous passive motion for articular cartilage healing and regeneration.

  1994cited by this paper
• The physiologic basis of continuous passive motion for articular cartilage healing and regeneration

  1994cited by this paper
• Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1.

  1994cited by this paper
• Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis.

  1994cited by this paper
• Cytokines and inflammation in cartilage degradation.

  1993cited by this paper
• The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats.

  1992cited by this paper
• Biological resurfacing of full-thickness defects in patellar articular cartilage of the rabbit. Investigation of autogenous periosteal grafts subjected to continuous passive motion.

  1992cited by this paper
• Role of metalloproteinases in human osteoarthritis.

  1991cited by this paper
• Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide.

  1991cited by this paper
• Effect of purified human interleukin‐1 on cartilage degradation

  1988cited by this paper
• Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint.

  1986cited by this paper

• Mechanical stimulation in 2D: A potent accelerator of matrix mineralization in ATDC5 chondrogenic cells.

  2025cites this paper
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  2025cites this paper
• Spectral characterization of cell surface motion for mechanistic investigations of cellular mechanobiology.

  2022cites this paper
• Chondrocyte De-Differentiation: Biophysical Cues to Nuclear Alterations

  2022cites this paper
• Advances in biomechanical and biochemical engineering methods to stimulate meniscus tissue.

  2021cites this paper
• Complications from Radiotherapy

  2020cites this paper
• Ex vivo physiological compression of human osteoarthritis cartilage modulates cellular and matrix components

  2019cites this paper
• Mechanical loading inhibits cartilage inflammatory signalling via an HDAC6 and IFT-dependent mechanism regulating primary cilia elongation

  2019cites this paper
• Biomechanical Stimulus Based Strategies for Meniscus Tissue Engineering and Regeneration

  2018cites this paper
• Effect of biomechanical stress on endogenous antioxidant networks in bovine articular cartilage

  2017cites this paper
• Histologic effects of mandibular protrusion splints in antigen-induced TMJ arthritis in rabbits

  2017cites this paper
• Effects of Inflammation on Multiscale Biomechanical Properties of Cartilaginous Cells and Tissues

  2017cites this paper
• Effects of mechanical stress on chondrocyte phenotype and chondrocyte extracellular matrix expression

  2016cites this paper
• Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

  2016cites this paper
• The TMSB4 Pseudogene LncRNA Functions as a Competing Endogenous RNA to Promote Cartilage Degradation in Human Osteoarthritis

  2016cites this paper
• Effects of Cyclic Tensile Strain on Chondrocyte Metabolism: A Systematic Review

  2015influential citation
• Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

  2015cites this paper
• Moderate cyclic tensile strain alters the assembly of cartilage extracellular matrix proteins in vitro.

  2015cites this paper
• Are cellular mechanosensors potential therapeutic targets in osteoarthritis

  2014cites this paper
• Extracellular matrix integrity affects the mechanical behaviour of in-situ chondrocytes under compression.

  2014cites this paper
• fibrochondrocytes proinflammatory gene induction in meniscal Dynamic biophysical strain modulates

  2013cites this paper
• THERAPEUTIC EXERCISE PRODUCES LESS PROINFLAMMATORY AND MORE ANTI-INFLAMMATORY CYTOKINES CAUSED BY OSTEOARTHRITIS

  2013cites this paper
• Molecular Effects of Exercise in Rheumatoid Arthritis

  2012cites this paper
• Mechanical Stretching of Cells of Different Tissues: The Role of Mediators of Innate Immunity

  2012cites this paper
• Identification of Mechanosensitive Genes in Chondrocytes and Osteoblasts and Their Role in OA Pathogenesis

  2012cites this paper
• Validation of an In Vitro Model to Study Human Cartilage Responses to Compression

  2012cites this paper
• Chapiter 10: Identification of mechanosensitive genes in chondrocytes and osteoblasts and their role in OA pathogenesis

  2012cites this paper
• Biomechanical Influence of Cartilage Homeostasis in Health and Disease

  2011cites this paper
• Mechanical Loading of Articular Cartilage Reduces IL-1-Induced Enzyme Expression

  2011cites this paper
• Mechanotransduction and cartilage integrity

  2011cites this paper
• The Mechanosensitivity of Cells in Joint Tissues: Role in the Pathogenesis of Joint Diseases

  2010cites this paper
• Effects of raised-intensity phonation on inflammatory mediator gene expression in normal rabbit vocal fold

  2010cites this paper
• Mechanical load inhibits IL-1 induced matrix degradation in articular

  2010cites this paper
• Wnt Signaling During Inflammation, Mechanical Stimulation and Differentiation

  2010cites this paper
• Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage.

  2010cites this paper
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  2009cites this paper
• Molecular effects of exercise in patients with inflammatory rheumatic disease

  2008cites this paper
• Dynamic compression counteracts IL-1β induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs

  2008cites this paper
• Intra-articular injection of interleukin-4 decreases nitric oxide production by chondrocytes and ameliorates subsequent destruction of cartilage in instability-induced osteoarthritis in rat knee joints.

  2008cites this paper
• Dynamic compression influences interleukin-1β-induced nitric oxide and prostaglandin E2 release by articular chondrocytes via alterations in iNOS and COX-2 expression

  2008cites this paper
• An analysis of the strain field in biaxial Flexcell membranes for different waveforms and frequencies

  2008cites this paper
• Regulation of biomechanical signals by NF-κB transcription factors in chondrocytes

  2008cites this paper
• Effects of tensile and compressive strains on response of a chondrocytic cell line embedded in type I collagen gel.

  2008cites this paper
• Edinburgh Dynamic compression counteracts IL-1 beta induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs

  2008cites this paper
• Physiologic deformational loading does not counteract the catabolic effects of interleukin-1 in long-term culture of chondrocyte-seeded agarose constructs.

  2008cites this paper
• Signal transduction pathways involving p38 MAPK, JNK, NFκB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1β and dynamic compression

  2008cites this paper
• IL-1 and iNOS gene expression and NO synthesis in the superior region of meniscal explants are dependent on the magnitude of compressive strains.

  2008cites this paper
• Regulation of chondrocytic gene expression by biomechanical signals.

  2008cites this paper
• Hyaluronic acid and chondroitin sulfate content of osteoarthritic human knee cartilage: Site‐specific correlation with weight‐bearing force based on femorotibial angle measurement

  2008cites this paper
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  2007cites this paper
• Elbow Passive Motion Rehabilitation Utilizing a Continuous Passive Motion Device following Surgical Release , Manipulation Under Anesthesia , or Post Stable Fracture : A Review

  2007cites this paper
• Nitric oxide synthase and cyclooxygenase interactions in cartilage and meniscus: relationships to joint physiology, arthritis, and tissue repair.

  2007cites this paper
• Clinical Guidelines for CPM following an ACL Reconstruction

  2007cites this paper
• Dynamic biomechanical strain inhibits IL-1beta-induced inflammation in vocal fold fibroblasts.

  2007cites this paper
• Biomechanical strain regulates TNFR2 but not TNFR1 in TMJ cells.

  2007cites this paper
• Dynamic biophysical strain modulates proinflammatory gene induction in meniscal fibrochondrocytes.

  2006cites this paper
• , Capsular Release or Post-Traumatic Stiffness ; A Review

  2006cites this paper
• Mechanobiology and cartilage engineering: The underlying pathophysiological phenomena

  2006cites this paper
• Elbow CPM Following a Stable Intra-Articular Fracture

  2006cites this paper
• Modulation of proteoglycan production by cyclic tensile stretch in intervertebral disc cells through a post-translational mechanism

  2006cites this paper
• Shoulder Passive Motion Rehabilitation Utilizing a Continuous Passive Motion Device following Surgical Release or Manipulation Under Anesthesia

  2006cites this paper
• Dynamic compression counteracts IL-1β induced iNOS and COX-2 activity by human chondrocytes cultured in agarose constructs

  2006cites this paper
• Cell and tissue engineering and clinical applications: An overview

  2006cites this paper
• CONTINUOUS PASSIVE MOTION REHABILITATION AFTER SURGERY FOR GLENOHUMERAL INSTABILITY

  2006cites this paper
• Association between subjective lameness grade and kinetic gait parameters in horses with experimentally induced forelimb lameness.

  2005cites this paper
• The influence of mechanical compression on the induction of osteoarthritis-related biomarkers in articular cartilage explants.

  2005cites this paper
• Extracellular superoxide dismutase and oxidant damage in osteoarthritis.

  2005cites this paper
• [Chondrocyte mecanobiology. Application in cartilage tissue engineering].

  2005cites this paper
• Vocal Fold Fibroblast Response to Mechanical Stress

  2005cites this paper
• Mécanobiologie du chondrocyte. Application à l’ingénierie du cartilage

  2005cites this paper
• Chondrocyte viability in press‐fit cryopreserved osteochondral allografts

  2004cites this paper
• Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals.

  2004cites this paper
• A central role for nuclear factor‐κB pathway in the antiinflammatory and proinflammatory actions of mechanical strain

  2003cites this paper
• The effects of mechanical strain on synovial fibroblasts.

  2003cites this paper
• Dynamic compression counteracts IL-1 beta-induced release of nitric oxide and PGE2 by superficial zone chondrocytes cultured in agarose constructs.

  2003cites this paper
• Signal transduction by mechanical strain in chondrocytes

  2003cites this paper
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  2003cites this paper
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  2003cites this paper
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  2003cites this paper
• Synthesis, Biodegradability, and Biocompatibility of Lysine Diisocyanate–Glucose Polymers

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• Drs. Gassner and Agarwal respond to Maloney, et al.'s article in the January 2002 issue of CRANIO.

  2002cites this paper
• Invited review: the mitochondrion in osteoarthritis.

  2002cites this paper
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  2001cites this paper
• Le cartilage : de la mécanobiologie au traitement physique

  2001cites this paper
• [Cartilage: from biomechanics to physical therapy].

  2001cites this paper
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  2001cites this paper
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  2001cites this paper
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  2001cites this paper
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  2000cites this paper
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  2000cites this paper
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  2000cites this paper
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  2000cites this paper
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  2000cites this paper
• A new peptide-based urethane polymer: synthesis, biodegradation, and potential to support cell growth in vitro.

  2000cites this paper
• Cartilage injury and repair.

  2000cites this paper
• Interaction of strain and interleukin-1 in articular cartilage: effects on proteoglycan synthesis in chondrocytes.

  2000cites this paper
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