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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Parker, Eleanor
Languages: English
Types: Doctoral thesis
Subjects: UOW2
Whilst mechanical impact is known to be essential for cartilage maintenance, it\ud has been noted that altered joint loading and increased force may lead to cartilage\ud degradation and increase the risk for the development of osteoarthritis (OA). This\ud study investigated the cellular responses of chondrocytes to mechanical impact,\ud and the effects of possible chondroprotective agents for OA preventative\ud strategies in individuals exposed to high impact, repetitive loading. Single-impact\ud mechanical trauma (force 1.14 N, pressure 6.47 KPa) was determined to induce\ud biphasic decrease in cell volume to 647.38±60.38 ?m3 at 2 h and 516.52±38.86\ud ?m3 at 48 h, the initial phase of which was observed to be an active\ud mechanotransduction mechanism, termed Impact-Induced Volume Decrease\ud (IIVD), and the subsequent phase to be Apoptotic Volume Decrease (AVD). The\ud newly defined IIVD was concluded to be dependent upon the PKC/PLC?3\ud pathway, and possibly mediated by intracellular Ca2+ store release and Volume\ud Sensitive Organic Anion Channel (VSOAC) activity. Furthermore, mechanical\ud impact was observed to induce a rapid decrease in F-actin from 1.19±0.13 MU to\ud 0.87±0.02 MU, termed Impact-Induced Actin Decrease (IIAD) and associated with\ud the biphasic rise in cell death at rates of 2.75±0.41 %.h-1 and 0.66±0.03 %.h-1.\ud Both in vivo exercise and in vitro mechanical load induced a release IL-1?\ud (20.67±2.58 % and 5.86±0.21 AU), MCP-1 (25.69±0.53 % and 1.45±0.01 AU) and\ud IL-10 (8.97±2.40 % and 5.55±0.28 AU), with in vivo concentrations correlating with\ud joint magnitude and strike patterns. Decreased levels of IL-1? and MCP-1 (to\ud 9.60±2.34 % and 9.01±2.34 %, respectively) observed in the evening were further\ud confirmed using a hyperosmotic-treated in vitro model of prolonged static-loaded\ud cartilage with evidence for a IL-1?-dominated paracrine loop between articular\ud cartilage and mononuclear phagocytes. In vitro, chondroprotective and antiinflammatory\ud actions of chondroitin sulphate, glucosamine sulphate, REV 5901\ud and Tamoxifen were associated with a reduction in pre-impact cell volume\ud (average of 31.91±4.19 %) and increased pre-impact actin levels (average of\ud 39.92±9.29 %). Anti-inflammatory agents, curcumin and dexamethasone exhibited\ud less effective chondroprotective actions, via inhibition of IL-1? (average of\ud 83.45±1.30 %) and thus apoptosis. To conclude, high impact exercise is\ud recommended with a place for chondroprotective properties of chondroitin,\ud glucosamine sulphate and/or curcumin in high-risk groups before OA onset.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 2. Parker E, Getting SJ, Hucklebridge F, Vleck V & Kerrigan MJP. The effects of REV5901 on chondrocyte viability following mechanical trauma. Proceedings of the British Pharmacological Society, Vol 7, Issue 4, abst127P, London, UK, 2009.
    • 3. Parker E, Noureen S, Getting SJ, Vleck VE, Hucklebridge F & Kerrigan MJP. REV5901: Chondroprotective Effects Post Mechanical Trauma. Proceeding of the Physiological Society Meeting 19, PC156, University of Manchester, UK, 2010.
    • 4. Parker E, Domah S, Getting SJ, Vleck VE, Hucklebridge F & Kerrigan MJP. Knee Forces And Inflammation: The Effects of Foot Strike Patterns And Footwear. Proceeding of the Physiological Society Meeting 19, PC176, University of Manchester, UK, 2010.
    • 5. Parker E, Begum N, Wunderlich C, Ravichandran N, Getting SJ, Vleck VE, Hucklebridge F & Kerrigan MJP Chondroitin And Glucosamine Supplementation Results In Increased Chondrocyte Viability Post Mechanical Trauma In Vitro. Proceeding of the Physiological Society Meeting 19, PC268, University of Manchester, UK, 2010.
    • 6. Parker E, Qusous A, Getting SJ, Hucklebridge F & Kerrigan MJP. Cartilage And Macrophages: Evidence For A Paracrine Loop.
    • 8. Parker EL, Peetroons C, Getting SJ, Hucklebridge F & Kerrigan MJP. Tamoxifen: chondroprotective effects post-mechanical trauma. Proceeding of the Physiological Society Meeting 21, PC33, University of Durham, UK, 2010.
    • SZCZODRY, M., COYLE, C., KRAMER, S., SMOLINSKI, P. & CHU, C. (2009) Progressive Chondrocyte Death After Impact Injury Indicates a Need for Chondroprotective Therapy. The American Journal of Sports Medicine.
    • TETLOW, L. C., ADLAM, D. J. & WOOLLEY, D. E. (2001) Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum, 44, 585-94.
    • TEW, S. R., KWAN, A. P., HANN, A., THOMSON, B. M. & ARCHER, C. W. (2000) The reactions of articular cartilage to experimental wounding: role of apoptosis. Arthritis Rheum, 43, 215-25.
    • THOMAS, K. & COLEMAN, P. (2004) Use of complementary or alternative medicine in a general population in Great Britain. Results from the National Omnibus survey. J Public Health (Oxf), 26, 152-7.
    • THOMAS, K. J., NICHOLL, J. P. & COLEMAN, P. (2001) Use and expenditure on complementary medicine in England: a population based survey. Complement Ther Med, 9, 2-11.
    • TOFT, A. D., JENSEN, L. B., BRUUNSGAARD, H., IBFELT, T., HALKJAER-KRISTENSEN, J., FEBBRAIO, M. & PEDERSEN, B. K. (2002) Cytokine response to eccentric exercise in young and elderly humans. Am J Physiol Cell Physiol, 283, C289-95.
    • TRAN-KHANH, N., HOEMANN, C. D., MCKEE, M. D., HENDERSON, J. E. & BUSCHMANN, M. D. (2005) Aged bovine chondrocytes display a diminished capacity to produce a collagen-rich, mechanically functional cartilage extracellular matrix. J Orthop Res, 23, 1354-62.
    • TRAUB, P. (1995) Intermediate filaments and gene regulation. Physiol Chem Phys Med NMR, 27, 377-400.
    • TRICKEY, W., VAIL, T. & GUILAK, F. (2004) The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes. Journal of Orthopaedic Research, 22, 131-139.
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