Mechanical loading and cartilage physiology

Parker, E. 2011. Mechanical loading and cartilage physiology. PhD thesis University of Westminster School of Life Sciences

TitleMechanical loading and cartilage physiology
TypePhD thesis
AuthorsParker, E.
Abstract

Whilst mechanical impact is known to be essential for cartilage maintenance, it

has been noted that altered joint loading and increased force may lead to cartilage degradation and increase the risk for the development of osteoarthritis (OA). This study investigated the cellular responses of chondrocytes to mechanical impact,

and the effects of possible chondroprotective agents for OA preventative

strategies in individuals exposed to high impact, repetitive loading. Single-impact mechanical trauma (force 1.14 N, pressure 6.47 KPa) was determined to induce

biphasic decrease in cell volume to 647.38±60.38 μm3 at 2 h and 516.52±38.86

μm3 at 48 h, the initial phase of which was observed to be an active

mechanotransduction mechanism, termed Impact-Induced Volume Decrease

(IIVD), and the subsequent phase to be Apoptotic Volume Decrease (AVD). The

newly defined IIVD was concluded to be dependent upon the PKC/PLCβ3

pathway, and possibly mediated by intracellular Ca2+ store release and Volume

Sensitive Organic Anion Channel (VSOAC) activity. Furthermore, mechanical

impact was observed to induce a rapid decrease in F-actin from 1.19±0.13 MU to

0.87±0.02 MU, termed Impact-Induced Actin Decrease (IIAD) and associated with

the biphasic rise in cell death at rates of 2.75±0.41 %.h-1 and 0.66±0.03 %.h-1. Both in vivo exercise and in vitro mechanical load induced a release IL-1β

(20.67±2.58 % and 5.86±0.21 AU), MCP-1 (25.69±0.53 % and 1.45±0.01 AU) and

IL-10 (8.97±2.40 % and 5.55±0.28 AU), with in vivo concentrations correlating with joint magnitude and strike patterns. Decreased levels of IL-1β and MCP-1 (to

9.60±2.34 % and 9.01±2.34 %, respectively) observed in the evening were further

confirmed using a hyperosmotic-treated in vitro model of prolonged static-loaded cartilage with evidence for a IL-1β-dominated paracrine loop between articular

cartilage and mononuclear phagocytes. In vitro, chondroprotective and antiinflammatory actions of chondroitin sulphate, glucosamine sulphate, REV 5901

and Tamoxifen were associated with a reduction in pre-impact cell volume

(average of 31.91±4.19 %) and increased pre-impact actin levels (average of

39.92±9.29 %). Anti-inflammatory agents, curcumin and dexamethasone exhibited

less effective chondroprotective actions, via inhibition of IL-1β (average of

83.45±1.30 %) and thus apoptosis. To conclude, high impact exercise is

recommended with a place for chondroprotective properties of chondroitin,

glucosamine sulphate and/or curcumin in high-risk groups before OA onset.

Year2011
FileEleanor_PARKER_2011.pdf
Publication dates
Completed2011

Related outputs

Novel methods for the quantification of changes in actin organization in chondrocytes using fluorescent imaging and linear profiling
Qusous, A., Parker, E., Geewan, C., Kapasi, A., Getting, S.J., Hucklebridge, F., Keshavarz, T. and Kerrigan, M.J.P. 2012. Novel methods for the quantification of changes in actin organization in chondrocytes using fluorescent imaging and linear profiling. Microscopy Research and Technique. 75 (7), pp. 991-999.

REV5901 induces calcium dependant chondroprotective effects post in vitro mechanical loading
Parker, E., Qusous, A., Getting, S.J., Hucklebridge, F. and Kerrigan, M.J.P. 2011. REV5901 induces calcium dependant chondroprotective effects post in vitro mechanical loading. ORS Annual Meeting vol. 36. Long Beach, California

Cartilage and macrophages: evidence for a paracrine loop. Poster no. 278
Parker, E., Qusous, A., Getting, S.J., Hucklebridge, F. and Kerrigan, M.J.P. 2010. Cartilage and macrophages: evidence for a paracrine loop. Poster no. 278. Combined Meeting of Orthopaedic Research Societies. Kyoto, Japan

Tamoxifen: chondroprotective effects post-mechanical trauma
Parker, E., Peetroons, C., Getting, S.J., Hucklebridge, F. and Kerrigan, M.J.P. 2010. Tamoxifen: chondroprotective effects post-mechanical trauma. Physiological Society Meeting 21. University of Durham

REV5901: chondroprotective effects post mechanical trauma
Parker, E., Noureen, S., Getting, S.J., Vleck, V.E., Hucklebridge, F. and Kerrigan, M.J.P. 2010. REV5901: chondroprotective effects post mechanical trauma. Physiological Society Meeting 19. University of Manchester

The effects of REV5901 on chondrocyte viability following mechanical trauma
Parker, E., Getting, S.J., Hucklebridge, F., Vleck, V.E. and Kerrigan, M.J.P. 2010. The effects of REV5901 on chondrocyte viability following mechanical trauma. British Orthopaedic Research Society Annual Meeting. Newcastle upon Tyne 22 - 23 Jun 2009 Wiley.

Diurnal inflammatory cytokine changes post-exercise. Poster no. 319
Parker, E., Getting, S.J., Hucklebridge, F. and Kerrigan, M.J.P. 2010. Diurnal inflammatory cytokine changes post-exercise. Poster no. 319. Combined Meeting of Orthopaedic Research Societies. Kyoto, Japan

Knee forces and inflammation: the effects of foot strike patterns and footwear
Parker, E., Domah, S., Getting, S.J., Vleck, V.E., Hucklebridge, F. and Kerrigan, M.J.P. 2010. Knee forces and inflammation: the effects of foot strike patterns and footwear. Physiological Society Meeting 19. University of Manchester

Chondroitin and glucosamine supplementation results in increased chondrocyte viability post mechanical trauma in vitro
Parker, E., Begum, N., Wunderlich, C., Ravichandran, N., Getting, S.J., Vleck, V.E., Hucklebridge, F. and Kerrigan, M.J.P. 2010. Chondroitin and glucosamine supplementation results in increased chondrocyte viability post mechanical trauma in vitro. Physiological Society Meeting 19. University of Manchester

The effects of REV5901 on chondrocyte viability following mechanical trauma
Parker, E., Getting, S.J., Hucklebridge, F., Vleck, V.E. and Kerrigan, M.J.P. 2009. The effects of REV5901 on chondrocyte viability following mechanical trauma. pA2 Online. From the Queen Elizabeth II Conference Centre London, Winter 2009 Meeting: Proceedings of the British Pharmacological Society. 7 (4), p. P0149.

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