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Long-term repetitive mechanical loading of the knee joint by in vivo muscle stimulation accelerates cartilage degeneration and increases chondrocyte death in a rabbit model

      Abstract

      Background

      Excessive chronic loading is thought to be one factor responsible for the onset of osteoarthritis. For example, studies using treadmill running have shown an increased risk for osteoarthritis, thereby suggesting that muscle-induced joint loading may play a role in osteoarthritis onset and progression. However, in these studies, muscle-induced loading was not carefully quantified. Here, we present a model of controlled muscular loading which allows for the accurate quantification of joint loading. The aim of this study was to evaluate the effects of long-term, cyclic, isometric and dynamic, muscle-induced joint loading of physiologic magnitude but excessive intensity on cartilage integrity and cell viability in the rabbit knee.

      Methods

      24 rabbits were divided into an (i) eccentric, (ii) concentric, or (iii) isometric knee extensor contraction group (50 min of cyclic, submaximal stimulation 3 times/week for four weeks = 19,500 cycles) controlled by the stimulation of a femoral nerve cuff electrode on the right hind limb. The contralateral knee was used as a non-loaded control. The knee articular cartilages were analysed by confocal microscopy for chondrocyte death, and histologically for Mankin Score, cartilage thickness and cell density.

      Findings

      All loaded knees had significantly increased cell death rates and Mankin Scores compared to the non-loaded joints. Cartilage thicknesses did not systematically differ between loaded and control joints.

      Interpretation

      Chondrocyte death and Mankin Scores were significantly increased in the loaded joints, thereby linking muscular exercise of physiologic magnitude but excessive intensity to cartilage degeneration and cell death in the rabbit knee.

      Keywords

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      References

        • Aigner T.
        • Zien A.
        • Gehrsitz A.
        • Gebhard P.
        • McKennam L.
        Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using complementary DNA-array technology.
        Arthritis Rheum. 2001; 44: 2777-2789
        • Bevill S.
        • Briant P.
        • Levenston M.
        • Andriacchi T.
        Central and peripheral region tibial plateau chondrocytes respond differently to in vitro dynamic compression.
        Osteoarthr. Cartil. 2009; 17: 980-987
        • Chen C.
        • Burton-Wurster N.
        • Lust G.
        • Bank R.
        • Tekoppele J.M.
        Compositional and metabolic changes in damaged cartilage are peak-stress, stress-rate, and loading-duration dependent.
        J. Orthop. Res. 1999; 17: 870-879
        • Chen C.
        • Burton-Wurster N.
        • Borden C.
        • Hueffer K.
        • Bloom S.
        • Lust G.
        Chondrocyte necrosis and apoptosis in impact damaged articular cartilage.
        J. Orthop. Res. 2001; 19: 703-711
        • Clark A.
        • Leonard T.
        • Barclay L.
        • Matyas J.
        • Herzog W.
        Opposing cartilages in the patellofemoral joint adapt differently to long-term cruciate deficiency: chondrocyte deformation and reorientation with compression.
        Osteoarthr. Cartil. 2005; 13: 1100-1114
        • Clements K.
        • Bee Z.
        • Crossingham G.
        • Adams M.
        • Sharif M.
        How severe must repetitive loading be to kill chondrocytes in articular cartilage?.
        Osteoarthr. Cartil. 2001; 9: 499-507
        • Duda G.
        • Eilers M.
        • Loh L.
        • Hoffman J.
        • Kääb M.
        • Schaser K.
        Chondrocyte death precedes structural damage in blunt impact trauma.
        Clin. Orthop. Rel. Res. 2001; 393: 302-309
        • Golenberg N.
        • Kepich E.
        • Haut R.C.
        Histomorphological and mechanical property correlations in rabbit tibial plateau cartilage based on a fibril- reinforced biphasic model.
        Int. J. Exp. Comput. Biomech. 2009; 1: 58-75
        • Hashimoto S.
        • Takahashi K.
        • Amiel D.
        • Coutts R.
        • Lotz M.
        Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis.
        Arthritis Rheum. 1998; 41: 1266-1274
        • Hasler E.
        • Herzog W.
        • Leonard T.
        • Stano A.
        • Nguyen H.
        In vivo knee joint loading and kinematics before and after ACL transection in an animal model.
        J. Biomech. 1998; 31: 253-262
        • Hayami T.
        • Pickarski M.
        • Zhuo Y.
        • Wesolowski G.
        • Rodan G.
        • Duong le T.
        Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.
        Bone. 2006; 38: 234-243
        • Herzog W.
        • Diet S.
        • Suter E.
        • Mayzus P.
        • Leonard T.
        • Müller C.
        • et al.
        Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis.
        J. Biomech. 1998; 31: 1137-1145
        • Herzog W.
        • Longino D.
        • Clark W.
        The role of muscles in joint adaptation and degeneration.
        Langenbecks Arch. Surg. 2003; 2088: 305-315
        • Hill A.
        The heat of shortening and the dynamic constants of muscle.
        Proc Biol Sci. 1938; 126: 136-195
        • Horisberger M.
        • Fortuna R.
        • Leonard T.
        • Valderrabano V.
        • Herzog W.
        The influence of cyclic concentric and eccentric submaximal muscle loading on cell viability in the rabbit knee joint.
        Clin. Biomech. 2012; 27: 292-298
        • Isaac D.
        • Meyer E.
        • Haut R.
        Chondrocyte damage and contact pressures following impact on the rabbit tibiofemoral joint.
        J. Biomech. Eng. 2008; 130 (041018-1-5)
        • Isaac D.
        • Meyer E.
        • Kopke K.
        • Haut R.
        Chronic changes in the rabbit tibial plateau following blunt trauma to the tibiofemoral joint.
        J. Biomech. 2010; 18: 1682-1688
        • Juncosa N.
        • West J.
        • Galloway M.
        • Boivin G.
        • Butler D.
        In vivo forces used to develop design parameters for tissue engineered implants for rabbit patellar tendon repair.
        J. Biomech. 2003; 36: 483-488
        • Koh T.
        • Leonard T.
        An implantable electrical interface for in vivo studies of the neuromuscular system.
        J. Neuroscience. 1996; 70: 27-32
        • Little C.
        • Ghosh P.
        Variation in proteoglycan metabolism by articular chondrocytes in different joint regions is determined by post-natal mechanical loading.
        Osteoarthr. Cartil. 1997; 5: 49-62
        • Loening A.
        • James I.
        • Levenston M.
        • Badger A.
        • Frank E.
        • Kurz B.
        • et al.
        Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis.
        Arch. Biochem. Biophys. 2000; 381: 205-512
        • Longino D.
        • Butterfield T.
        • Herzog W.
        Frequency and length-dependent effects of Botulinum toxin-induced muscle weakness.
        J. Biomech. 2005; 38: 609-613
        • Longino D.
        • Frank C.
        • Leonard T.
        • Herzog W.
        Proposed model of botulinum toxin-induced muscle weakness in the rabbit.
        J. Orthop. Res. 2005; 23: 1404-1410
        • Mankin H.
        • Dorfman H.
        • Lipiello L.
        • Zarins A.
        Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic hips.
        J. Bone Joint Surg. 1971; 53: 523-537
        • Newton P.
        • Mow V.
        • Gardner T.
        • Buckwalter J.
        • Albright J.
        Winner of the 1996 Cabaud Award. The effect of lifelong exercise on canine articular cartilage.
        Am. J. Sports Med. 1997; 25: 282-287
        • Pandy M.
        • Andriacchi T.
        Muscle and joint function in human locomotion.
        Annu. Rev. Biomed. Eng. 2010; 12: 401-433
        • Poole C.
        • Gilbert R.
        • Herbage D.
        • Hartmann D.
        Immunolocalization of type IX collagen in normal and spontaneously osteoarthritic canine tibial cartilage and isolated chondrons.
        Osteoarthr. Cartil. 1997; 5: 191-204
        • Radin E.
        • Martin R.
        • Burr D.
        • Caterson B.
        • Boyd R.
        • Goodwin C.
        Effects of mechanical loading on the tissues of the rabbit knee.
        J. Orthop. Res. 1984; 2: 221-234
        • Rehan Youssef A.
        • Longino D.
        • Seerattan R.
        • Leonard T.
        • Herzog W.
        Muscle weakness causes joint degeneration in rabbits.
        Osteoarthr. Cartil. 2009; 17: 1228-1235
        • Roemhildt M.
        • Coughlin K.
        • Peura G.
        • Fleming B.
        • Beynnon B.
        Material properties of articular cartilage in the rabbit tibial plateau.
        J. Biomech. 2006; 39: 2331-2337
        • Roemhildt M.
        • Coughlin K.
        • Peura G.
        • Badger G.
        • Churchill D.
        • Fleming B.
        • et al.
        Effects of increased chronic loading on articular cartilage material properties in the lapine tibio-femoral joint.
        J. Biomech. 2010; 26: 2301-2308
        • Roemhildt M.
        • Beynnon B.
        • Gardner-Morse M.
        • Badger G.
        • Grant C.
        Changes induced by chronic in vivo load alteration in the tibiofemoral joint of mature rabbits.
        J. Orthop. Res. 2012; 30: 1413-1422
        • Roos E.M.
        • Herzog W.
        • Block J.A.
        • Bennell K.
        Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis.
        Nat. Rev. Rheumatol. 2011; 7: 57-63
        • Sun H.
        Mechanical loading, cartilage degradation, and arthritis.
        Ann. N. Y. Acad. Sci. 2010; 1211: 37-50
        • Szczodry M.
        • Coyle C.
        • Kramer S.
        • Smolinski P.
        • Chu C.
        Progressive chondrocyte death after impact injury indicates a need for chondroprotective therapy.
        Am. J. Sports Med. 2009; 37: 2318-2322
        • Tew S.
        • Kwan A.
        • Hann A.
        • Thomson B.
        • Archer C.
        The reactions of articular cartilage to experimental wounding: role of apoptosis.
        Arthritis Rheum. 2000; 43: 215-225
        • van der Sluijs J.
        • Geesink R.
        • van der Linden A.
        • Bulstra S.
        • Kuyer R.
        • Drukker J.
        The reliability of the Mankin score for osteoarthritis.
        J. Orthop. Res. 1992; 10: 58-61
        • Vasan N.
        Effects of physical stress on the synthesis and degradation of cartilage matrix.
        Connect. Tissue Res. 1983; 12: 49-58
        • Winby C.
        • Lloyd D.
        • Besier T.
        • Kirk T.
        Muscle and external load contribution to knee joint contact loads during normal gait.
        J. Biomech. 2009; 42: 2294-2300