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Mechanosensitive Purinergic Calcium Signalling in Articular Chondrocytes

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Book cover Mechanosensitive Ion Channels

Part of the book series: Mechanosensitivity in Cells and Tissues ((MECT,volume 1))

Abstract

Mechanotransduction is the mechanism through which living cells sense and respond to mechanical stimuli. In many tissues, including muscle, blood vessel, bone, ligament and cartilage, mechanotransduction is essential for tissue health and function. Although mechanotransduction mechanisms have been identified in a number of tissues, the signalling pathways have not yet been elucidated in articular cartilage. This chapter explores the influence of physiological mechanical stimuli on intracellular Ca2+ signalling in articular chondrocytes and its potential involvement in cartilage mechanotransduction. The review focuses primarily on Ca2+ signalling activated by deformation of isolated primary articular chondrocytes cultured within the well-established agarose model system. The chapter discusses the involvement of a mechanosensitive purinergic pathway which trigger Ca2+ signalling through the release of ATP and the activation of purine receptors. The influence of different loading parameters on the Ca2+ signalling characteristics is discussed as a putative mechanism through which cells differentiate between different loading conditions. Finally the chapter examines the downstream cellular response to mechanically-activated purinergic Ca2+ signalling and its importance in tissue health and homeostasis

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References

  • Aydelotte M, Keuttner KE (1988). Differences between sub-populations of cultured bovine articular chondrocytes. I. Morphology and cartilage matrix production. Connect Tissue Res 18:205–222.

    PubMed  CAS  Google Scholar 

  • Behrens F, Kraft EL, Oegema TR (1989). Biochemical changes in articular cartilage after joint immobilisation by casting or external fixation. Journal of Orthopaedic Research 7:335–343.

    Article  PubMed  CAS  Google Scholar 

  • Benninghoff A (1925). Form und Bau der Gelenknorpel in ihren Beziehungen zur Funktion. Zeitschrift fur Zellforschung und mikroskopische Anatomie 2:783–789.

    Article  Google Scholar 

  • Berridge MJ, Bootman MD, Lipp P (1998). Calcium - a life and death signal. Nature 395:645–648.

    Article  PubMed  CAS  Google Scholar 

  • Berridge MJ, Lipp P, Bootman MD (2000). The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21.

    Article  PubMed  CAS  Google Scholar 

  • Bodin P, Burnstock G (2001). Purinergic signalling: ATP release. Neurochem Res 26:959–969.

    Article  PubMed  CAS  Google Scholar 

  • Bootman MD, Lipp P, Berridge MJ (2001). The organisation and functions of local Ca(2+) signals. J Cell Sci 114:2213–2222.

    PubMed  CAS  Google Scholar 

  • Boudreault F, Grygorczyk R (2002). Cell swelling-induced ATP release and gadolinium-sensitive channels. Am J Physiol Cell Physiol 282C:219–226.

    Google Scholar 

  • Bourret LA, Rodan GA (1976). The role of calcium in the inhibition of cAMP accunulated in epiphyseal cartilage cells exposed to physiological pressure. Journal of Cellular Physiology 88:353–362.

    Article  PubMed  CAS  Google Scholar 

  • Boyde A, Jones SJ (1983). Scanning electron microscopy of cartilage. In: Boyde A, editor. Cartilage: Structure, Function and Biochemistry.Acedemic Press. p. 105–148.

    Google Scholar 

  • Browning JA, Saunders K, Urban JP, Wilkins RJ (2004). The influence and interactions of hydrostatic and osmotic pressures on the intracellular milieu of chondrocytes. Biorheology 41:299–308.

    PubMed  CAS  Google Scholar 

  • Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB (1995). Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci 108: 1497–1508.

    PubMed  CAS  Google Scholar 

  • Buschmann MD, Kim YJ, Wong M, Frank E, Hunziker EB, Grodzinsky AJ (1999). Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow. Arch Biochem Biophys 366:1–7.

    Article  PubMed  CAS  Google Scholar 

  • Caswell AM, Leong WS, Russell RG (1991). Evidence for the presence of P2-purinoceptors at the surface of human articular chondrocytes in monolayer culture. Biochim Biophys Acta 1074:151–158.

    PubMed  CAS  Google Scholar 

  • Chao PH, West AC, Hung CT (2006). Chondrocyte Intracellular Calcium, Cytoskeletal Organization and Gene Expression Responses to Dynamic Osmotic Loading. Am J Physiol Cell Physiol. In Press.

    Google Scholar 

  • Chowdhury TT, Bader DL, Shelton JC, Lee DA (2003). Temporal regulation of chondrocyte metabolism in agarose constructs subjected to dynamic compression. Arch Biochem Biophys 417:105–111.

    Article  PubMed  CAS  Google Scholar 

  • Chowdhury TT, Knight MM (2006). Purinergic pathway suppresses the release of (.)NO and stimulates proteoglycan synthesis in chondrocyte/agarose constructs subjected to dynamic compression. J Cell Physiol . In Press.

    Google Scholar 

  • D’Andrea P, Calabrese A, Capozzi I, Grandolfo M, Tonon R, Vittur F (2000). Intercellular Ca2+ waves in mechanically stimulated articular chondrocytes. Biorheology 37:75–83.

    PubMed  CAS  Google Scholar 

  • Edlich M, Yellowley CE, Jacobs CR, Donahue HJ (2001). Oscillating fluid flow regulates cytosolic calcium concentration in bovine articular chondrocytes. J Biomech 34:59–65.

    Article  PubMed  CAS  Google Scholar 

  • Edlich M, Yellowley CE, Jacobs CR, Donahue HJ (2004). Cycle number and waveform of fluid flow affect bovine articular chondrocytes. Biorheology 41:315–322.

    PubMed  CAS  Google Scholar 

  • Elfervig MK, Graff RD, Lee GM, Kelley SS, Sood A, Banes AJ (2001). ATP induces Ca(2+) signaling in human chondrons cultured in three-dimensional agarose films. Osteoarthritis Cartilage 9:518–526.

    Article  PubMed  CAS  Google Scholar 

  • Erickson GR, Alexopoulos LG, Guilak F (2001). Hyper-osmotic stress induces volume change and calcium transients in chondrocytes by transmembrane, phospholipid, and G-protein pathways. J Biomech 34:1527–1535.

    Article  PubMed  CAS  Google Scholar 

  • Erickson GR, Northrup DL, Guilak F (2003). Hypo-osmotic stress induces calcium-dependent actin reorganization in articular chondrocytes. Osteoarthritis Cartilage 11:187–197.

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald JB, Jin M, Dean D, Wood DJ, Zheng MH, Grodzinsky AJ (2004). Mechanical compression of cartilage explants induces multiple time-dependent gene expression patterns and involves intracellular calcium and cyclic AMP. J Biol Chem 279:19502–19511.

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald JB, Jin M, Grodzinsky AJ (2006). Shear and compression differentially regulate clusters of functionally related temporal transcription patterns in cartilage tissue. J Biol Chem 281:24095–24103.

    Article  PubMed  CAS  Google Scholar 

  • Graff RD, Lazarowski ER, Banes AJ, Lee GM (2000). ATP release by mechanically loaded porcine chondrons in pellet culture. Arthritis Rheum 43:1571–1579.

    Article  PubMed  CAS  Google Scholar 

  • Grodzinsky AJ, Levenston ME, Jin M, Frank EH (2000). Cartilage tissue remodeling in response to mechanical forces. Annu Rev Biomed Eng 2:691–713.

    Article  PubMed  CAS  Google Scholar 

  • Guilak F, Ratcliffe A, Mow VC (1995). Chondrocyte Deformation and local tissue strain in articular cartilage: A confocal microscopy study. J Orthop Res 13:410–421.

    Article  PubMed  CAS  Google Scholar 

  • Guilak F, Zell RA, Erickson GR, Grande DA, Rubin CT, McLeod KJ, Donahue HJ (1999). Mechanically induced calcium waves in articular chondrocytes are inhibited by gadolinium and amiloride. J Orthop Res 17:421–429.

    Article  PubMed  CAS  Google Scholar 

  • Hatori M, Teixeira CC, Debolt K, Pacifici M, Shapiro IM (1995). Adenine nucleotide metabolism by chondrocytes in vitro: role of ATP in chondrocyte maturation and matrix mineralization. J Cell Physiol 165:468–474.

    Article  PubMed  CAS  Google Scholar 

  • Hauselmann HJ, Fernandes RJ, Mok SS, Schmid TM, Block JA, Aydelotte MB, Kuettner KE, Thonar JMA (1994). Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads. Journal of Cell Science 107:17–27.

    PubMed  Google Scholar 

  • Hoebertz A, Townsend-Nicholson A, Glass R, Burnstock G, Arnett TR (2000). Expression of P2 receptors in bone and cultured bone cells. Bone 27:503–510.

    Article  PubMed  CAS  Google Scholar 

  • Hung CT, Mauck RL, Wang CC, Lima EG, Ateshian GA (2004). A paradigm for functional tissue engineering of articular cartilage via applied physiologic deformational loading. Ann Biomed Eng 32:35–49.

    Article  PubMed  Google Scholar 

  • Kempson GE, Freeman MAR, Swanson SAV (1971). The determination of creep modulus for articular cartilage from indentation tests on the human femoral head. Journal of Biomechanics 4:239-50.

    Article  PubMed  CAS  Google Scholar 

  • Kiviranta I, Jurvelin J, Tammi M, Saamanen A, Helminen HJ (1987). Weight bearing controls glycosaminoglycan concentration and articular cartilage thickness in the knee joints of young beagle dogs. Arthritis and Rheumatism 30:801–809.

    Article  PubMed  CAS  Google Scholar 

  • Knight MM, Bomzon Z, Kimmel E, Sharma A.M., Lee DA, Bader DL (2006). Chondrocyte deformation induces mitochondrial distortion and heterogeneous intracellular strain fields. Biomechanics and Modeling in Mechanobiology 5:180–191.

    Article  PubMed  CAS  Google Scholar 

  • Knight MM, Lee DA, Bader DL (1998). The influence of elaborated pericellular matrix on the deformation of isolated articular chondrocytes cultured in agarose. Biochim Biophys Acta 1405:67–77.

    Article  PubMed  CAS  Google Scholar 

  • Knight MM, Lee DA, Bader DL (1996). Distribution of chondrocyte deformation in compressed agarose gel using confocal microscopy. Journal of Cellular Engineering 1:97–102.

    Google Scholar 

  • Knight MM, Toyoda T, Lee DA, Bader DL (2005). Mechanical compression and hydrostatic pressure induce reversible changes in actin cytoskeletal organisation in chondrocytes in agarose. J Biomech 39:1547–1551.

    Article  PubMed  Google Scholar 

  • Kono T, Nishikori T, Kataoka H, Uchio Y, Ochi M, Enomoto K (2006). Spontaneous oscillation and mechanically induced calcium waves in chondrocytes. Cell Biochem Funct 24:103–111.

    Article  PubMed  CAS  Google Scholar 

  • Koolpe M, Benton HP (1997). Calcium-mobilizing purine receptors on the surface of mammalian articular chondrocytes. J Orthop Res 15:204–212.

    Article  PubMed  CAS  Google Scholar 

  • Koolpe M, Pearson D, Benton HP (1999). Expression of both P1 and P2 purine receptor genes by human articular chondrocytes and profile of ligand-mediated prostaglandin E2 release. Arthritis Rheum 42:258–267.

    Article  PubMed  CAS  Google Scholar 

  • Lee DA, Bader DL (1997). Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose. J Orthop Res 15:181–188.

    Article  PubMed  Google Scholar 

  • Lee DA, Knight MM (2004). Mechanical Loading of Chondrocytes Embedded in 3D Constructs: In Vitro Methods for Assessment of Morphological and Metabolic Response to Compressive Strain. Methods Mol Med 100:307–324.

    PubMed  CAS  Google Scholar 

  • Lee DA, Knight MM, Bolton JF, Idowu BD, Kayser MV, Bader DL (2000). Chondrocyte deformation within compressed agarose constructs at the cellular and sub-cellular levels. J Biomech 33:81–95.

    Article  PubMed  CAS  Google Scholar 

  • Leong WS, Russell RG, Caswell AM (1994). Stimulation of cartilage resorption by extracellular ATP acting at P2-purinoceptors. Biochim Biophys Acta 1201:298–304.

    PubMed  CAS  Google Scholar 

  • Li KW, Klein TJ, Chawla K, Nugent GE, Bae WC, Sah RL (2004). In vitro physical stimulation of tissue-engineered and native cartilage. Methods Mol Med 100:325–352.

    PubMed  Google Scholar 

  • Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, Hung CT, Ateshian GA (2000). Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 2000:252–260.

    Article  Google Scholar 

  • McKnight NL, Frangos JA (2003). Strain rate mechanotransduction in aligned human vascular smooth muscle cells. Ann Biomed Eng 31:239–249.

    Article  PubMed  Google Scholar 

  • Millward-Sadler SJ, Salter DM (2004). Integrin-dependent signal cascades in chondrocyte mechanotransduction. Ann Biomed Eng 32:435–446.

    Article  PubMed  CAS  Google Scholar 

  • Millward-Sadler SJ, Wright MO, Flatman PW, Salter DM (2004). ATP in the mechanotransduction pathway of normal human chondrocytes. Biorheology 41:567–575.

    PubMed  CAS  Google Scholar 

  • Mizuno S (2005). A novel method for assessing effects of hydrostatic fluid pressure on intracellular calcium: a study with bovine articular chondrocytes. Am J Physiol Cell Physiol 288: C329–C337.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno S, Tateishi T, Ushida T, Glowacki J (2002). Hydrostatic fluid pressure enhances matrix synthesis and accumulation by bovine chondrocytes in three-dimensional culture. J Cell Physiol 193:319–327.

    Article  PubMed  CAS  Google Scholar 

  • Mobasheri A, Martin-Vasallo P (1999). Epithelial sodium channels in skeletal cells: a role in mechanotransduction ? Cell Biology International 23:237–240.

    Article  PubMed  CAS  Google Scholar 

  • Ohashi T, Hagiwara M, Bader DL, Knight MM (2006). Intracellular mechanics and mechanotransduction associated with chondrocyte deformation during pipette aspiration. Biorheology 43:201–214.

    PubMed  CAS  Google Scholar 

  • Palmoski MJ, Brandt KD (1984). Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis and Rheumatism 27:675–681.

    Article  PubMed  CAS  Google Scholar 

  • Pingguan-Murphy B, El-Azzeh M, Bader DL, Knight MM (2006). Cyclic compression of chondrocytes modulates a purinergic calcium signalling pathway in a strain rate- and frequency-dependent manner. J Cell Physiol 209:389–397.

    Article  PubMed  CAS  Google Scholar 

  • Pingguan-Murphy B, Lee DA, Bader DL, Knight MM (2005). Activation of chondrocytes calcium signalling by dynamic compression is independent of number of cycles. Arch Biochem Biophys 444:45–51.

    Article  PubMed  CAS  Google Scholar 

  • Poole CA, Flint MH, Beaumont BW (1985). Analysis of the morphology and function of primary cilia in connective tissues: a cellular cybernetic probe? Cell Motil 5:175–193.

    Article  PubMed  CAS  Google Scholar 

  • Praetorius HA, Spring KR (2005). A physiological view of the primary cilium. Annu Rev Physiol 67:515–529.

    Article  PubMed  CAS  Google Scholar 

  • Ralevic V, Burnstock G (1998). Receptors for purines and pyrimidines. Pharmacol Rev 50: 413–492.

    PubMed  CAS  Google Scholar 

  • Roberts SR, Knight MM, Lee DA, Bader DL (2001). Mechanical compression influences intracellular Ca2+ signaling in chondrocytes seeded in agarose constructs. J Appl Physiol 90:1385–1391.

    PubMed  CAS  Google Scholar 

  • Sah R, Kim Y, Doong J, Grodzinsky AJ, Plaas AHK, Sandy JD (1989). Biosynthetic response of cartilage explants to dynamic compression. J Orthop Res 7:619–636.

    Article  PubMed  CAS  Google Scholar 

  • Seidel JO, Pei M, Gray ML, Langer R, Freed LE, Vunjak-Novakovic G (2004). Long-term culture of tissue engineered cartilage in a perfused chamber with mechanical stimulation. Biorheology 41:445–458.

    PubMed  CAS  Google Scholar 

  • Surprenant A, Rassendren F, Kawashima E, North RA, Buell G (1996). The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272:735–738.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka N, Ohno S, Honda K, Tanimoto K, Doi T, Ohno-Nakahara M, Tafolla E, Kapila S, Tanne K (2005). Cyclic mechanical strain regulates the PTHrP expression in cultured chondrocytes via activation of the Ca2+ channel. J Dent Res 84:64–68.

    Article  PubMed  CAS  Google Scholar 

  • Toyoda T, Seedhom BB, Kirkham J, Bonass WA (2003). Upregulation of aggrecan and type II collagen mRNA expression in bovine chondrocytes by the application of hydrostatic pressure. Biorheology 40:79–85.

    PubMed  CAS  Google Scholar 

  • Trickey WR, Vail TP, Guilak F (2004). The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes. J Orthop Res 22:131–139.

    Article  PubMed  Google Scholar 

  • Urban JPG (1994). The chondrocyte: A cell under pressure. Br J Rheumatol 33:901–908.

    Article  PubMed  CAS  Google Scholar 

  • Valhmu WB, Stazzone EJ, Bachrach NM, Saed-Nejad F, Fischer SG, Mow VC, Ratcliffe A (1998). Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch Biochem Biophys 1998 May 1; 353:29–36.

    Article  CAS  Google Scholar 

  • Wilkins RJ, Fairfax TP, Davies ME, Muzyamba MC, Gibson JS (2003). Homeostasis of intracellular Ca2+ in equine chondrocytes: response to hypotonic shock. Equine Vet J 35:439–443.

    Article  PubMed  CAS  Google Scholar 

  • Wright M, Jobanputra P, Bavington C, Salter DM, Nuki G (1996). Effects of intermittent pressure-induced strain on the electrophysiology of cultured human chondrocytes: evidence for the presence of stretch-activated membrane ion channels. Clinical Science 90:61–71.

    PubMed  CAS  Google Scholar 

  • Yellowley CE, Hancox JC, Donahue HJ (2002). Effects of cell swelling on intracellular calcium and membrane currents in bovine articular chondrocytes. J Cell Biochem 86:290–301.

    Article  PubMed  CAS  Google Scholar 

  • Yellowley CE, Jacobs CR, Donahue HJ (1999). Mechanisms contributing to fluid-flow-induced Ca2+ mobilization in articular chondrocytes. J Cell Physiol 180:402–408.

    Article  PubMed  CAS  Google Scholar 

  • Zhang M, Wang JJ, Chen YJ (2005). Effects of mechanical pressure on intracellular calcium release channel and cytoskeletal structure in rabbit mandibular condylar chondrocytes. Life Sci 78:2480–2487.

    Article  PubMed  CAS  Google Scholar 

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Pingguan-Murphy, B., Knight, M.M. (2008). Mechanosensitive Purinergic Calcium Signalling in Articular Chondrocytes. In: Kamkin, A., Kiseleva, I. (eds) Mechanosensitive Ion Channels. Mechanosensitivity in Cells and Tissues, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6426-5_10

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