Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis

References

• Martin JA, Buckwalter JA. The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. J Bone Joint Surg Am. 2003;85-A(Suppl 2):106–110.
   Google Scholar
• Price FM, Levick JR, Mason RM. Changes in glycosaminoglycan concentration and synovial permeability at raised intra-articular pressure in rabbit knees. J Physiol. 1996;495(3):821–833.
   PubMed Web of Science ®Google Scholar
• Levick JR. Microvascular architecture and exchange in synovial joints. Microcirculation. 1995 Sep;2(3):217–233.
   PubMedGoogle Scholar
• Coleman PJ, Scott D, Abiona A, et al. Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit knee synovium. J Physiol. 1998;509(3):695–710.
   PubMed Web of Science ®Google Scholar
• Scott D, Coleman PJ, Mason RM, et al. Direct evidence for the partial reflection of hyaluronan molecules by the lining of rabbit knee joints during trans-synovial flow. J Physiol. 1998;508(2):619–623.
   PubMed Web of Science ®Google Scholar
• Coleman PJ, Scott D, Mason RM, et al. Role of hyaluronan chain length in buffering interstitial flow across synoviumin rabbits. J Physiol. 2000;526(2):425–434.
   PubMed Web of Science ®Google Scholar
• Scott D, Coleman PJ, Mason RM, et al. Action of polysaccharides of similar average mass but differing molecular volume and charge on fluid drainage through synovial interstitium in rabbit knees. J Physiol. 2000 Nov 1;528(Pt 3):609–618.
   PubMed Web of Science ®Google Scholar
• Scott D, Coleman PJ, Mason RM, et al. Concentration dependence of interstitial flow buffering by hyaluronan in synovial joints. Microvasc Res. 2000 May;59(3):345–353.
   PubMed Web of Science ®Google Scholar
• Scott D, Bertin K, Poli Aet al. Interstitial pressure gradients around joints; location of chief resistance to fluid drainage from the rabbit knee. Exp Physiol. 2001;86:739–747.
   PubMed Web of Science ®Google Scholar
• Lu Y, Levick JR, Wang W. The mechanism of synovial fluid retention in pressurized joint cavities. Microcirculation. 2005 Oct-Nov;12(7):581–595.
   PubMed Web of Science ®Google Scholar
• Momberger TS, Levick JR, Mason RM. Hyaluronan secretion by synoviocytes is mechanosensitive. Matrix Biol. 2005 Dec;24(8):510–519.
   PubMed Web of Science ®Google Scholar
• Momberger TS, Levick JR, Mason RM. Mechanosensitive synoviocytes: a Ca2+ -PKCalpha-MAP kinase pathway contributes to stretch-induced hyaluronan synthesis in vitro. Matrix Biol. 2006 Jul;25(5):306–316.
   PubMed Web of Science ®Google Scholar
• Large RJ, Hollywood MA, Sergeant GP, et al. Ionic currents in intimal cultured synoviocytes from the rabbit. Am J Physiol Cell Physiol. 2010 Nov;299(5):C1180–94.
   PubMed Web of Science ®Google Scholar
• Ingram KR, Wann AK, Angel CK, et al. Cyclic movement stimulates hyaluronan secretion into the synovial cavity of rabbit joints. J Physiol. 2008 Mar 15;586(6):1715–1729.
   PubMed Web of Science ®Google Scholar
• Ingram KR, Wann AK, Wingate RM, et al. Signal pathways regulating hyaluronan secretion into static and cycled synovial joints of rabbits. J Physiol. 2009 Sep 1;587(Pt 17):4361–4376.
   PubMed Web of Science ®Google Scholar
• Huang J, Ballou LR, Hasty KA. Cyclic equibiaxial tensile strain induces both anabolic and catabolic responses in articular chondrocytes. Gene. 2007 Dec 1;404(1–2):101–109.
   PubMed Web of Science ®Google Scholar
• Kaupp JA, Weber JF, Waldman SD. Mechanical stimulation of chondrocyte-agarose hydrogels. J Vis Exp. 2012 Oct;27(68):e4229.
   Google Scholar
• Wohlrab D, Wohlrab J, Reichel H, et al. Is the proliferation of human chondrocytes regulated by ionic channels? J Orthop Sci. 2001;6:155–159.
   PubMedGoogle Scholar
• Mouw JK, Imler SM, Levenston ME. Ion-channel regulation of chondrocyte matrix synthesis in 3D culture under static and dynamic compression. Biomech Model Mechanobiol. 2007 Jan;6(1–2):33–41.
   PubMed Web of Science ®Google Scholar
• Zhu M, Zhou S, Huang Z, et al. Ca2+-dependent endoplasmic reticulum stress regulates mechanical stress-mediated cartilage thinning. J Dent Res. 2016 Jul;95(8):889–896.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Yamamura H, Imaizumi Y, et al. K(+) and Ca(2+) channels regulate Ca(2+) signaling in chondrocytes: an illustrated review. Cells. 2020 Jun 29;9(7). DOI:https://doi.org/10.3390/cells9071577.
   Google Scholar
• Xu BY, Jin Y, Ma XH, et al. The potential role of mechanically sensitive ion channels in the physiology, injury, and repair of articular cartilage. J Orthop Surg. 2020;28(3):2309499020950262. .
   Web of Science ®Google Scholar
• Mobasheri A, Carter SD, Martin-Vasallo P, et al. Integrins and stretch activated ion channels; putative components of functional cell surface mechanoreceptors in articular chondrocytes. Cell Biol Int. 2002;26(1):1–18.
   PubMed Web of Science ®Google Scholar
• Chowdhury TT, Knight MM. Purinergic pathway suppresses the release of .NO and stimulates proteoglycan synthesis in chondrocyte/agarose constructs subjected to dynamic compression. J Cell Physiol. 2006 Dec;209(3):845–853.
   PubMed Web of Science ®Google Scholar
• Li J, Zhao Q, Wang E, et al. Dynamic compression of rabbit adipose-derived stem cells transfected with insulin-like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis. J Cell Physiol. 2012 May;227(5):2003–2012.
   PubMed Web of Science ®Google Scholar
• Das P, Schurman DJ, Lane Smith R. Nitric oxide and G proteins mediate the response of bovine articular chondrocytes to fluid-induced shear. J Orthop Res. 1997;15(1):87–93.
   PubMed Web of Science ®Google Scholar
• Asmar A, Barrett-Jolley R, Werner A, et al. Membrane channel gene expression in human costal and articular chondrocytes. Organogenesis. 2016 Apr 2;12(2):94–107.
   PubMed Web of Science ®Google Scholar
• O’Neil RG, Heller S. The mechanosensitive nature of TRPV channels. Pflugers Arch. 2005 Oct;451(1):193–203.
   PubMed Web of Science ®Google Scholar
• Clark AL, Votta BJ, Kumar S, et al. Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4: age- and sex-dependent progression of osteoarthritis in Trpv4-deficient mice. Arthritis Rheum. 2010 Oct;62(10):2973–2983.
   PubMedGoogle Scholar
• Guilak F, Leddy HA, Liedtke W. Transient receptor potential vanilloid 4: the sixth sense of the musculoskeletal system? Ann N Y Acad Sci. 2010 Mar;1192:404–409.
   PubMed Web of Science ®Google Scholar
• Hall AC, Horwitz ER, Wilkins RJ. The cellular physiology of articular cartilage. Exp Physiol. 1996;81(3):535–545.
   PubMed Web of Science ®Google Scholar
• Tanaka N, Ohno S, Honda K, et al. Cyclic mechanical strain regulates the PTHrP expression in cultured chondrocytes via activation of the Ca2+ channel. J Dent Res. 2005;84:64–68.
   PubMed Web of Science ®Google Scholar
• O’Conor CJ, Leddy HA, Benefield HC, et al. TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Natl Acad Sci U S A. 2014;111:1316–1321.
   PubMed Web of Science ®Google Scholar
• Srinivasan PP, Parajuli A, Price C, et al. Inhibition of T-type voltage sensitive calcium channel reduces load-induced OA in mice and suppresses the catabolic effect of bone mechanical stress on chondrocytes. PloS One. 2015;10(5):e0127290. .
   PubMed Web of Science ®Google Scholar
• Servin-Vences MR, Moroni M, Lewin GR, et al. Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. Elife. 2017 Jan 30;6. DOI:https://doi.org/10.7554/eLife.21074.
   Google Scholar
• Ji Q, He C. Extracorporeal shockwave therapy promotes chondrogenesis in cartilage tissue engineering: a hypothesis based on previous evidence. Med Hypotheses. 2016 Jun;91:9–15.
   PubMed Web of Science ®Google Scholar
• Coleman MC, Ramakrishnan PS, Brouillette MJ, et al. Injurious loading of articular cartilage compromises chondrocyte respiratory function. Arthritis Rheumatol (Hoboken). 2016 Mar;68(3):662–671. .
   PubMed Web of Science ®Google Scholar
• Dolzani P, Assirelli E, Pulsatelli L, et al. Ex vivo physiological compression of human osteoarthritis cartilage modulates cellular and matrix components. PloS One. 2019;14(9):e0222947. .
   PubMed Web of Science ®Google Scholar
• Lin YY, Tanaka N, Ohkuma S, et al. Applying an excessive mechanical stress alters the effect of subchondral osteoblasts on chondrocytes in a co-culture system. Eur J Oral Sci. 2010 Apr;118(2):151–158. .
   PubMed Web of Science ®Google Scholar
• Mobasheri A, Lewis R, Ferreira-Mendes A, et al. Potassium channels in articular chondrocytes. Channels. 2012 Nov-Dec;6(6):416–425. .
   PubMed Web of Science ®Google Scholar
• Kachroo U, Livingston A, Vinod E, et al. Comparison of electrophysiological properties and gene expression between human chondrocytes and chondroprogenitors derived from normal and osteoarthritic cartilage. Cartilage. 2020 Jul;11(3):374–384. .
   PubMed Web of Science ®Google Scholar
• Sun HB. Mechanical loading, cartilage degradation, and arthritis. Ann N Y Acad Sci. 2010 Nov;1211:37–50.
   PubMed Web of Science ®Google Scholar
• Chen C, Tambe DT, Deng L, et al. Biomechanical properties and mechanobiology of the articular chondrocyte. Am J Physiol Cell Physiol. 2013 Dec 15;305(12):C1202–8.
   PubMed Web of Science ®Google Scholar
• Matta C, Mobasheri A, Gergely P, et al. Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game. Cell Signal. 2014 Oct;26(10):2175–2185. .
   PubMed Web of Science ®Google Scholar
• Blain EJ. Involvement of the cytoskeletal elements in articular cartilage homeostasis and pathology. Int J Exp Pathol. 2009 Feb;90(1):1–15.
   PubMed Web of Science ®Google Scholar
• Milner CE, Meardon SA, Hawkins JL, et al. Walking velocity and step length adjustments affect knee joint contact forces in healthy weight and obese adults. J Orthop Res. 2018 Oct;36(10):2679–2686.
   PubMed Web of Science ®Google Scholar
• Ma Y, Song Y, Li L, et al. Mechano growth factor pretreatment yield mechanical stimuli induced cell stress responses in ligament fibroblasts of osteoarthritis via activating ATF-2. Biotechnol Lett. 2020 Aug;42(8):1337–1349.
   PubMed Web of Science ®Google Scholar
• Silawal S, Triebel J, Bertsch T, et al. Osteoarthritis and the complement cascade. Clin Med Insights. 2018;11:1179544117751430. .
   Google Scholar
• Wong S, Chiu K, Yan C. Review article: osteophytes. J Orthop Surg. 2016;24(3):403–410.
   Web of Science ®Google Scholar
• Van Der Kraan PM, Van Den Berg WB. Osteophytes: relevance and biology. Osteoarthritis Cartilage. 2007;15(3):237–244.
   PubMed Web of Science ®Google Scholar
• Venne G, Tse MY, Pang SC, et al. Mechanically-induced osteophyte in the rat knee. Osteoarthritis Cartilage. 2020 Jun;28(6):853–864.
   PubMed Web of Science ®Google Scholar
• Mobasheri A, Mobasheri R, Francis MJ, et al. Ion transport in chondrocytes: membrane transporters involved in intracellular ion homeostasis and the regulation of cell volume, free [Ca2+] and pH. Histol Histopathol. 1998;13:893–910.
   PubMed Web of Science ®Google Scholar
• Valhmu WB, Raia FJ. myo-Inositol 1,4,5-trisphosphate and Ca2+/calmodulin-dependent factors mediate transduction of compression-induced signals in bovine articular chondrocytes. Biochem J. 2002;361:689–696.
   PubMed Web of Science ®Google Scholar
• Ramage L, Nuki G, Salter DM. Signalling cascades in mechanotransduction: cell-matrix interactions and mechanical loading. Scand J Med Sci Sports. 2009 Aug;19(4):457–469.
   PubMed Web of Science ®Google Scholar
• Servin-Vences MR, Richardson J, Lewin GR, et al. Mechanoelectrical transduction in chondrocytes. Clin Exp Pharmacol Physiol. 2018 May;45(5):481–488.
   PubMed Web of Science ®Google Scholar
• Lee HS, Millward-Sadler SJ, Wright MO, et al. Integrin and mechanosensitive ion channel-dependent tyrosine phosphorylation of focal adhesion proteins and beta-catenin in human articular chondrocytes after mechanical stimulation. J Bone Miner Res. 2000 Aug;15(8):1501–1509.
   PubMed Web of Science ®Google Scholar
• Wang JH, Thampatty BP. An introductory review of cell mechanobiology. Biomech Model Mechanobiol. 2006 Mar;5(1):1–16.
   PubMed Web of Science ®Google Scholar
• Zhao Z, Li Y, Wang M, et al. Mechanotransduction pathways in the regulation of cartilage chondrocyte homoeostasis. J Cell Mol Med. 2020 May;24(10):5408–5419.
   PubMed Web of Science ®Google Scholar
• Satir P, Christensen ST. Overview of structure and function of mammalian cilia. Annu Rev Physiol. 2007;69:377–400.
   PubMed Web of Science ®Google Scholar
• Barrett-Jolley R, Lewis R, Fallman R, et al. The emerging chondrocyte channelome. Front Physiol. 2010;1:135.
   PubMed Web of Science ®Google Scholar
• Lee W, Guilak F, Liedtke W. Role of piezo channels in joint health and injury. Curr Top Membr. 2017;79:263–273.
   PubMed Web of Science ®Google Scholar
• Nourse JL, Pathak MM. How cells channel their stress: interplay between Piezo1 and the cytoskeleton. Semin Cell Dev Biol. 2017 Nov;71:3–12.
   PubMed Web of Science ®Google Scholar
• Trujillo E, Alvarez De La Rosa D, Mobasheri A, et al. Sodium transport systems in human chondrocytes. II. Expression of ENaC, Na+/K+/2Cl- cotransporter and Na+/H+ exchangers in healthy and arthritic chondrocytes. Histol Histopathol. 1999 Oct;14(4):1023–1031.
   PubMed Web of Science ®Google Scholar
• Millward-Sadler SJ, Wright MO, Lee H, et al. Altered electrophysiological responses to mechanical stimulation and abnormal signalling through alpha5beta1 integrin in chondrocytes from osteoarthritic cartilage. Osteoarthritis Cartilage. 2000 Jul;8(4):272–278.
   PubMed Web of Science ®Google Scholar
• Salter DM, Millward-Sadler SJ, Nuki G, et al. Integrin–interleukin-4 mechanotransduction pathways in human chondrocytes. Clin Orthop Relat Res. 2001;391:49–60.
   Google Scholar
• Knight MM, Toyoda T, Lee DA, et al. Mechanical compression and hydrostatic pressure induce reversible changes in actin cytoskeletal organisation in chondrocytes in agarose. J Biomech. 2006;39(8):1547–1551. .
   PubMed Web of Science ®Google Scholar
• Zhang M, Wang JJ, Chen YJ. Effects of mechanical pressure on intracellular calcium release channel and cytoskeletal structure in rabbit mandibular condylar chondrocytes. Life Sci. 2006 Apr 18;78(21):2480–2487.
   PubMed Web of Science ®Google Scholar
• Liu D, Yi C, Wang K, et al. Reorganization of cytoskeleton and transient activation of Ca2+ channels in mesenchymal stem cells cultured on silicon nanowire arrays. ACS Appl Mater Interfaces. 2013 Dec 26;5(24):13295–13304.
   PubMed Web of Science ®Google Scholar
• Shakibaei M, Mobasheri A. Beta1-integrins co-localize with Na, K-ATPase, epithelial sodium channels (ENaC) and voltage activated calcium channels (VACC) in mechanoreceptor complexes of mouse limb-bud chondrocytes. Histol Histopathol. 2003 Apr;18(2):343–351.
   PubMed Web of Science ®Google Scholar
• Mobasheri A, Barrett-Jolley R, Shakibaei M, et al. Enigmatic roles of the epithelial sodium channel (ENaC) in articular chondrocytes and osteoblasts: mechanotransduction, sodium transport or extracellular sodium sensing? In: Kamkin A, Kiseleva I, editors. Mechanosensitivity in Cells and Tissues. Moscow: Academia Copyright © 2005, Academia Publishing House Ltd; 2005.
   Google Scholar
• Abdul Kadir L, Stacey M, Barrett-Jolley R. Emerging roles of the membrane potential: action beyond the action potential. Front Physiol. 2018;9:1661.
   PubMed Web of Science ®Google Scholar
• Hammami S, Willumsen NJ, Meinild AK, et al. Purinergic signalling - a possible mechanism for KCNQ1 channel response to cell volume challenges. Acta Physiol. 2013 Mar;207(3):503–515.
   PubMed Web of Science ®Google Scholar
• Fodor J, Matta C, Olah T, et al. Store-operated calcium entry and calcium influx via voltage-operated calcium channels regulate intracellular calcium oscillations in chondrogenic cells. Cell Calcium. 2013 Jul;54(1):1–16.
   PubMed Web of Science ®Google Scholar
• Inayama M, Suzuki Y, Yamada S, et al. Orai1-Orai2 complex is involved in store-operated calcium entry in chondrocyte cell lines. Cell Calcium. 2015 May;57(5–6):337–347.
   PubMed Web of Science ®Google Scholar
• Gong X, Li G, Huang Y, et al. Synergistically regulated spontaneous calcium signaling is attributed to cartilaginous extracellular matrix metabolism. J Cell Physiol. 2019 Jun;234(6):9711–9722.
   PubMed Web of Science ®Google Scholar
• Lunz V, Romanin C, Frischauf I. STIM1 activation of Orai1. Cell Calcium. 2019 Jan;77:29–38.
   PubMed Web of Science ®Google Scholar
• Liu S, Takahashi M, Kiyoi T, et al. Genetic manipulation of calcium release-activated calcium channel 1 modulates the multipotency of human cartilage-derived mesenchymal stem cells. J Immunol Res. 2019;2019:7510214.
   PubMed Web of Science ®Google Scholar
• Somogyi CS, Matta C, Foldvari Z, et al. Polymodal transient receptor potential vanilloid (TRPV) ion channels in chondrogenic cells. Int J Mol Sci. 2015 Aug 7;16(8):18412–18438.
   PubMed Web of Science ®Google Scholar
• McNulty AL, Leddy HA, Liedtke W, et al. TRPV4 as a therapeutic target for joint diseases. Naunyn-Schmiedeberg’s Arch Pharmacol. 2015 Apr;388(4):437–450.
   Google Scholar
• Sanchez JC, Lopez-Zapata DF. The role of BKCa channels on hyperpolarization mediated by hyperosmolarity in human articular chondrocytes. Gen Physiol Biophys. 2011 Mar;30(1):20–27.
   PubMed Web of Science ®Google Scholar
• Kobayakawa T, Takahashi N, Sobue Y, et al. Mechanical stress loading induces CD44 cleavage in human chondrocytic HCS-2/8 cells. Biochem Biophys Res Commun. 2016 Sep 23;478(3):1230–1235.
   PubMed Web of Science ®Google Scholar
• Parisi C, Chandaria VV, Nowlan NC. Blocking mechanosensitive ion channels eliminates the effects of applied mechanical loading on chick joint morphogenesis. Philos Trans R Soc Lond B Biol Sci. 2018 Sep 24;373(1759):20170317.
   PubMed Web of Science ®Google Scholar
• Mobasheri A, Matta C, Uzieliene I, et al. The chondrocyte channelome: a narrative review. Joint Bone Spine. 2019 Jan;86(1):29–35.
   PubMed Web of Science ®Google Scholar
• Karamesinis K, Spyropoulou A, Dalagiorgou G, et al. Continuous hydrostatic pressure induces differentiation phenomena in chondrocytes mediated by changes in polycystins, SOX9, and RUNX2. J Orofac Orthop. 2017 Jan;78(1):21–31.
   PubMed Web of Science ®Google Scholar
• Du G, Li L, Zhang X, et al. Roles of TRPV4 and piezo channels in stretch-evoked Ca(2+) response in chondrocytes. Exp Biol Med. 2020 Feb;245(3):180–189.
   Web of Science ®Google Scholar
• Lv M, Zhou Y, Chen X, et al. Calcium signaling of in situ chondrocytes in articular cartilage under compressive loading: roles of calcium sources and cell membrane ion channels. J Orthop Res. 2018 Feb;36(2):730–738.
   PubMed Web of Science ®Google Scholar
• Yellowley CE, Jacobs CR, Zy LI, et al. Effects of fluid flow on intracellular calcium in bovine articular chondrocytes. Physiology. 1997.
   Web of Science ®Google Scholar
• Perkins GL, Derfoul A, Ast A, et al. An inhibitor of the stretch-activated cation receptor exerts a potent effect on chondrocyte phenotype. Differentiation. 2005;73:199–211.
   PubMed Web of Science ®Google Scholar
• Ponce A, Jimenez-Peña L, Tejeda-Guzman C. The role of swelling-activated chloride currents (I(CL,swell)) in the regulatory volume decrease response of freshly dissociated rat articular chondrocytes. Cell Physiol Biochem. 2012;30(5):1254–1270.
   PubMedGoogle Scholar
• Wang Z, Irianto J, Kazun S, et al. The rate of hypo-osmotic challenge influences regulatory volume decrease (RVD) and mechanical properties of articular chondrocytes. Osteoarthritis Cartilage. 2015 Feb;23(2):289–299.
   PubMed Web of Science ®Google Scholar
• Yellowley CE, Hancox JC, Donahue HJ. Effects of cell swelling on intracellular calcium and membrane currents in bovine articular chondrocytes. J Cell Biochem. 2002;86(2):290–301.
   PubMed Web of Science ®Google Scholar
• Sanchez JC, Wilkins RJ. Changes in intracellular calcium concentration in response to hypertonicity in bovine articular chondrocytes. Comp Biochem Physiol Part A Mol Integr Physiol. 2004 Jan;137(1):173–182.
   PubMed Web of Science ®Google Scholar
• Wu QQ, Chen Q. Mechanoregulation of chondrocyte proliferation, maturation, and hypertrophy: ion-channel dependent transduction of matrix deformation signals. Exp Cell Res. 2000 May 1;256(2):383–391.
   PubMed Web of Science ®Google Scholar
• Sánchez JC, Wilkins RJ. Effects of hypotonic shock on intracellular pH in bovine articular chondrocytes. Comp Biochem Physiol Part A. 2003;135(4):575–583.
   PubMed Web of Science ®Google Scholar
• Sánchez JC, Powell T, Staines HM, et al. Electrophysiological demonstration of voltage-activated H+ channels in bovine articular chondrocytes. Cell Physiol Biochem. 2006;18:85–90.
   PubMedGoogle Scholar
• Mobasheri A, Gent TC, Womack MD, et al. Quantitative analysis of voltage-gated potassium currents from primary equine (Equus caballus) and elephant (Loxodonta africana) articular chondrocytes. Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R172–80.
   PubMed Web of Science ®Google Scholar
• Funabashi K, Ohya S, Yamamura H, et al. Accelerated Ca2+ entry by membrane hyperpolarization due to Ca2+-activated K+ channel activation in response to histamine in chondrocytes. Am J Physiol Cell Physiol. 2010 Apr;298(4):C786–97.
   PubMed Web of Science ®Google Scholar
• Mobasheri A, Lewis R, Maxwell JE, et al. Characterization of a stretch-activated potassium channel in chondrocytes. J Cell Physiol. 2010 May;223(2):511–518.
   PubMed Web of Science ®Google Scholar
• Clausen MV, Jarerattanachat V, Carpenter EP, et al. Asymmetric mechanosensitivity in a eukaryotic ion channel. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8343–e8351.
   PubMed Web of Science ®Google Scholar
• Sanchez JC, Lopez-Zapata DF. Effects of osmotic challenges on membrane potential in human articular chondrocytes from healthy and osteoarthritic cartilage. Biorheology. 2010;47(5–6):321–331.
   PubMed Web of Science ®Google Scholar
• Hdud IM, Mobasheri A, Loughna PT. Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes. Am J Physiol Cell Physiol. 2014 Jun 1;306(11):C1050–7.
   PubMed Web of Science ®Google Scholar
• Liedtke W. TRPV4 plays an evolutionary conserved role in the transduction of osmotic and mechanical stimuli in live animals. J Physiol. 2005 Aug 15;567(Pt 1):53–58.
   PubMed Web of Science ®Google Scholar
• Guilak F. Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 2011 Dec;25(6):815–823.
   PubMed Web of Science ®Google Scholar
• Xu B, Xing R, Huang Z, et al. Excessive mechanical stress induces chondrocyte apoptosis through TRPV4 in an anterior cruciate ligament-transected rat osteoarthritis model. Life Sci. 2019 Jul 1;228:158–166.
   PubMed Web of Science ®Google Scholar
• Lee W, Leddy HA, Chen Y, et al. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc Natl Acad Sci U S A. 2014;111:5114–5122.
   Web of Science ®Google Scholar
• Apte SS. Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis. Biochem J. 2016 Jan 1;473(1):e1–4.
   PubMedGoogle Scholar
• Yang CY, Chanalaris A, Troeberg L. ADAMTS and ADAM metalloproteinases in osteoarthritis - looking beyond the ‘usual suspects’. Osteoarthritis Cartilage. 2017 Jul;25(7):1000–1009.
   PubMed Web of Science ®Google Scholar
• Zelenski NA, Leddy HA, Sanchez-Adams J, et al. Type VI collagen regulates pericellular matrix properties, chondrocyte swelling, and mechanotransduction in mouse articular cartilage. Arthritis Rheumatol. 2015 May;67(5):1286–1294.
   PubMed Web of Science ®Google Scholar
• Li C, Cao Z, Li W, et al. A review on the wide range applications of hyaluronic acid as a promising rejuvenating biomacromolecule in the treatments of bone related diseases. Int J Biol Macromol. 2020 Dec 15;165(Pt A):1264–1275.
   PubMedGoogle Scholar
• Kodama K, Takahashi H, Oiji N, et al. CANT1 deficiency in a mouse model of Desbuquois dysplasia impairs glycosaminoglycan synthesis and chondrocyte differentiation in growth plate cartilage. FEBS Open Bio. 2020 Jun;10(6):1096–1103.
   PubMed Web of Science ®Google Scholar
• Eleswarapu SV, Athanasiou KA. TRPV4 channel activation improves the tensile properties of self-assembled articular cartilage constructs. Acta Biomater. 2013 Mar;9(3):5554–5561.
   PubMed Web of Science ®Google Scholar
• Fu S, Meng H, Inamdar S, et al. Activation of TRPV4 by mechanical, osmotic or pharmaceutical stimulation is anti-inflammatory blocking IL-1β mediated articular cartilage matrix destruction. Osteoarthritis Cartilage. 2021 Jan;29(1):89–99.
   PubMed Web of Science ®Google Scholar
• Lewis R, Feetham CH, Barrett-Jolley R. Cell volume regulation in chondrocytes. Cell Physiol Biochem. 2011;28(6):1111–1122.
   PubMed Web of Science ®Google Scholar
• Ogawa Y, Takahashi N, Takemoto T, et al. Hyaluronan promotes TRPV4-induced chondrogenesis in ATDC5 cells. PloS One. 2019;14(8):e0219492.
   PubMed Web of Science ®Google Scholar
• Garcia-Elias A, Mrkonjic S, Jung L, et al. The TRPV4 channel. Cation Channels. 2014:293–319.
   Google Scholar
• O’Conor CJ, Ramalingam S, Zelenski NA, et al. Cartilage-specific knockout of the mechanosensory ion channel trpv4 decreases age-related osteoarthritis. Sci Rep. 2016 Jul 8;6:29053.
   PubMed Web of Science ®Google Scholar
• O’Conor CJ, Griffin TM, Liedtke W, et al. Increased susceptibility of Trpv4-deficient mice to obesity and obesity-induced osteoarthritis with very high-fat diet. Ann Rheum Dis. 2013 Feb;72(2):300–304.
   PubMed Web of Science ®Google Scholar
• Darby WG, Grace MS, Baratchi S, et al. Modulation of TRPV4 by diverse mechanisms. Int J Biochem Cell Biol. 2016 Sep;78:217–228.
   PubMed Web of Science ®Google Scholar
• Xing R, Wang P, Zhao L, et al. Mechanism of TRPA1 and TRPV4 participating in mechanical hyperalgesia of rat experimental knee osteoarthritis. Arch Rheumatol. 2017 Jun;32(2):96–104.
   PubMed Web of Science ®Google Scholar
• Krupkova O, Zvick J, Wuertz-Kozak K. The role of transient receptor potential channels in joint diseases. Eur Cell Mater. 2017 10;Oct(34):180–201.
   Google Scholar
• Richter F, Segond Von Banchet G, Schaible HG. Transient receptor potential vanilloid 4 ion channel in C-fibres is involved in mechanonociception of the normal and inflamed joint. Sci Rep. 2019 Jul 29;9(1):10928.
   PubMedGoogle Scholar
• Zhang XF, Chen J, Faltynek CR, et al. Transient receptor potential A1 mediates an osmotically activated ion channel. Eur J Neurosci. 2008 Feb;27(3):605–611.
   PubMed Web of Science ®Google Scholar
• Moilanen LJ, Hamalainen M, Nummenmaa E, et al. Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice–potential role of TRPA1 in osteoarthritis. Osteoarthritis Cartilage. 2015 Nov;23(11):2017–2026.
   PubMed Web of Science ®Google Scholar
• Nummenmaa E, Hämäläinen M, Pemmari A, et al. Transient receptor potential ankyrin 1 (TRPA1) is involved in upregulating interleukin-6 expression in osteoarthritic chondrocyte models. Int J Mol Sci. 2020 Dec 23;22:1.
   Web of Science ®Google Scholar
• Lewis R, Asplin KE, Bruce G, et al. The role of the membrane potential in chondrocyte volume regulation. J Cell Physiol. 2011 Nov;226(11):2979–2986.
   PubMed Web of Science ®Google Scholar
• Lewis AH, Grandl J. Inactivation kinetics and mechanical gating of Piezo1 ion channels depend on subdomains within the cap. Cell Rep. 2020 Jan 21;30(3):870–880.e2.
   PubMed Web of Science ®Google Scholar
• Yang QN, Cao Y, Zhou YW, et al. Expression characteristics of Piezo1 protein in stress models of human degenerative chondrocytes. China J Orthop Traumato. 2018:550–555.
   Google Scholar
• Ridone P, Pandzic E, Vassalli M, et al. Disruption of membrane cholesterol organization impairs the activity of PIEZO1 channel clusters. J Gen Physiol. 2020 Aug 3;152(8). DOI:https://doi.org/10.1085/jgp.201912515.
   Google Scholar
• Brohawn SG, Su Z, MacKinnon R. Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels. Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3614–3619.
   PubMed Web of Science ®Google Scholar
• Syeda R, Florendo MN, Cox CD, et al. Piezo1 channels are inherently mechanosensitive. Cell Rep. 2016 Nov 8;17(7):1739–1746.
   PubMed Web of Science ®Google Scholar
• Kefauver JM, Ward AB, Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels. Nature. 2020 Nov;587(7835):567–576.
   PubMed Web of Science ®Google Scholar
• Lewis AH, Cui AF, McDonald MF, et al. Transduction of repetitive mechanical stimuli by Piezo1 and Piezo2 ion channels. Cell Rep. 2017 Jun 20;19(12):2572–2585.
   PubMed Web of Science ®Google Scholar
• Ellefsen KL, Holt JR, Chang AC, et al. Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca(2+) flickers. Commun Biol. 2019;2:298.
   PubMed Web of Science ®Google Scholar
• Shin KC, Park HJ, Kim JG, et al. The Piezo2 ion channel is mechanically activated by low-threshold positive pressure. Sci Rep. 2019 Apr 23;9(1):6446.
   PubMedGoogle Scholar
• Zheng W, Nikolaev YA, Gracheva EO, et al. Piezo2 integrates mechanical and thermal cues in vertebrate mechanoreceptors. Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17547–17555.
   PubMed Web of Science ®Google Scholar
• Zhou T, Gao B, Fan Y, et al. Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-β-catenin. Elife. 2020 Mar 18;9. DOI:https://doi.org/10.7554/eLife.52779.
   Google Scholar
• Li XF, Zhang Z, Chen ZK, et al. Piezo1 protein induces the apoptosis of human osteoarthritis-derived chondrocytes by activating caspase-12, the signaling marker of ER stress. Int J Mol Med. 2017 Sep;40(3):845–853.
   PubMed Web of Science ®Google Scholar
• Lawrence KM, Jones RC, Jackson TR, et al. Chondroprotection by urocortin involves blockade of the mechanosensitive ion channel Piezo1. Sci Rep. 2017 Jul 11;7(1):5147.
   PubMedGoogle Scholar
• Millward-Sadler SJ, Wright MO, Flatman PW, et al. ATP in the mechanotransduction pathway of normal human chondrocytes. Biorheology. 2004;41(3–4):567–575.
   PubMed Web of Science ®Google Scholar
• Wei L, Mousawi F, Li D, et al. Adenosine triphosphate release and P2 receptor signaling in Piezo1 channel-dependent mechanoregulation. Front Pharmacol. 2019;10:1304.
   PubMed Web of Science ®Google Scholar
• Zeng D, Yao P, Zhao H. P2X7, a critical regulator and potential target for bone and joint diseases. J Cell Physiol. 2019 Mar;234(3):2095–2103.
   PubMed Web of Science ®Google Scholar
• Shimazaki A, Wright MO, Elliot K, et al. Calcium/calmodulin-dependent protein kinase II in human articular chondrocytes. Biorheology. 2006;43(3,4):223–233.
   PubMed Web of Science ®Google Scholar
• Ugawa S, Ishida Y, Ueda T, et al. Hypotonic stimuli enhance proton-gated currents of acid-sensing ion channel-1b. Biochem Biophys Res Commun. 2008 Mar 14;367(3):530–534.
   PubMed Web of Science ®Google Scholar
• Yamamura H, Suzuki Y, Imaizumi Y. Physiological and pathological functions of Cl(-) channels in chondrocytes. Biol Pharm Bull. 2018;41(8):1145–1151.
   PubMed Web of Science ®Google Scholar
• Tian M, Duan Y, Duan X. Chloride channels regulate chondrogenesis in chicken mandibular mesenchymal cells. Arch Oral Biol. 2010 Dec;55(12):938–945.
   PubMed Web of Science ®Google Scholar
• Kittl M, Winklmayr M, Helm K, et al. Acid- and volume-sensitive chloride currents in human chondrocytes. Front Cell Dev Biol. 2020;8:583131.
   PubMed Web of Science ®Google Scholar
• Isoya E, Toyoda F, Imai S, et al. Swelling-activated Cl(-) current in isolated rabbit articular chondrocytes: inhibition by arachidonic acid. J Pharmacol Sci. 2009 Feb;109(2):293–304.
   PubMed Web of Science ®Google Scholar
• Tsuga K, Tohse N, Yoshino M, et al. Chloride conductance determining membrane potential of rabbit articular chondrocytes. J Membr Biol. 2002 Jan 1;185(1):75–81.
   PubMed Web of Science ®Google Scholar
• Yamada S, Suzuki Y, Bernotiene E, et al. Swelling-activated ClC-3 activity regulates prostaglandin E(2) release in human OUMS-27 chondrocytes. Biochem Biophys Res Commun. 2021 Jan 22;537:29–35.
   PubMed Web of Science ®Google Scholar
• Kumagai K, Toyoda F, Staunton CA, et al. Activation of a chondrocyte volume-sensitive Cl(-) conductance prior to macroscopic cartilage lesion formation in the rabbit knee anterior cruciate ligament transection osteoarthritis model. Osteoarthritis Cartilage. 2016 Oct;24(10):1786–1794.
   PubMed Web of Science ®Google Scholar
• Kurita T, Yamamura H, Suzuki Y, et al. The ClC-7 chloride channel is downregulated by hypoosmotic stress in human chondrocytes. Mol Pharmacol. 2015 Jul;88(1):113–120.
   PubMed Web of Science ®Google Scholar
• Okumura N, Imai S, Toyoda F, et al. Regulatory role of tyrosine phosphorylation in the swelling-activated chloride current in isolated rabbit articular chondrocytes. J Physiol. 2009 Aug 1;587(Pt 15):3761–3776.
   PubMed Web of Science ®Google Scholar
• Lewis R, Feetham CH, Gentles L, et al. Benzamil sensitive ion channels contribute to volume regulation in canine chondrocytes. Br J Pharmacol. 2013 Apr;168(7):1584–1596.
   PubMed Web of Science ®Google Scholar
• Gessmann R, Kourtis N, Petratos K, et al. Molecular modeling of mechanosensory ion channel structural and functional features. PloS One. 2010 Sep 16;5(9):e12814.
   PubMed Web of Science ®Google Scholar
• Sabaratnam S, Arunan V, Coleman PJ, et al. Size selectivity of hyaluronan molecular sieving by extracellular matrix in rabbit synovial joints. J Physiol. 2005 Sep 1;567(Pt 2):569–581.
   PubMed Web of Science ®Google Scholar
• Sabaratnam S, Coleman PJ, Mason RM, et al. Interstitial matrix proteins determine hyaluronan reflection and fluid retention in rabbit joints: effect of protease. J Physiol. 2007 Jan 1;578(Pt 1):291–299.
   PubMed Web of Science ®Google Scholar
• Wuest SL, Calio M, Wernas T, et al. Influence of mechanical unloading on articular chondrocyte dedifferentiation. Int J Mol Sci. 2018;19(5):1289.
   PubMed Web of Science ®Google Scholar
• Nomura M, Sakitani N, Iwasawa H, et al. Thinning of articular cartilage after joint unloading or immobilization. An experimental investigation of the pathogenesis in mice. Osteoarthritis Cartilage. 2017 May;25(5):727–736.
   PubMed Web of Science ®Google Scholar
• Bertram KL, Banderali U, Tailor P, et al. Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells. Channels. 2016;10(2):148–157.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Ohya S, Yamamura H, et al. A new splice variant of large conductance Ca2+-activated K+ (BK) channel alpha subunit alters human chondrocyte function. J Biol Chem. 2016 Nov 11;291(46):24247–24260.
   PubMed Web of Science ®Google Scholar
• He BH, Christin M, Mouchbahani-Constance S, et al. Mechanosensitive ion channels in articular nociceptors drive mechanical allodynia in osteoarthritis. Osteoarthritis Cartilage. 2017 Dec;25(12):2091–2099.
   PubMed Web of Science ®Google Scholar
• Raouf R, Lolignier S, Sexton JE, et al. Inhibition of somatosensory mechanotransduction by annexin A6. Sci Signal. 2018;11(535):eaao2060.
   PubMed Web of Science ®Google Scholar
• Ikeuchi M, Izumi M, Aso K, et al. Effects of intra-articular hyaluronic acid injection on immunohistochemical characterization of joint afferents in a rat model of knee osteoarthritis. Eur J Pain. 2015 Mar;19(3):334–340.
   PubMed Web of Science ®Google Scholar
• Kuduk SD, Di Marco CN, Bodmer-Narkevitch V, et al. Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567. ACS Chem Neurosci. 2010 Jan 20;1(1):19–24.
   PubMed Web of Science ®Google Scholar
• Izumi M, Ikeuchi M, Ji Q, et al. Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis. J Biomed Sci. 2012 Aug 21;19(1):77.
   PubMedGoogle Scholar
• Schuelert N, Zhang C, Mogg AJ, et al. Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain. Osteoarthritis Cartilage. 2010 Nov;18(11):1536–1543.
   PubMed Web of Science ®Google Scholar
• Lewis R, Barrett-Jolley R. Changes in membrane receptors and ion channels as potential biomarkers for osteoarthritis. Front Physiol. 2015;6:357.
   PubMed Web of Science ®Google Scholar
• Cox CD, Bavi N, Martinac B. Biophysical principles of ion-channel-mediated mechanosensory transduction. Cell Rep. 2019 Oct 1;29(1):1–12.
   PubMed Web of Science ®Google Scholar
• Uddin SMZ, Komatsu DE. Therapeutic potential low-intensity pulsed ultrasound for osteoarthritis: pre-clinical and clinical perspectives. Ultrasound Med Biol. 2020 Apr;46(4):909–920.
   PubMed Web of Science ®Google Scholar
• Nasb M, Liangjiang H, Gong C, et al. Human adipose-derived Mesenchymal stem cells, low-intensity pulsed ultrasound, or their combination for the treatment of knee osteoarthritis: study protocol for a first-in-man randomized controlled trial. BMC Musculoskelet Disord. 2020 Jan 15;21(1):33.
   PubMed Web of Science ®Google Scholar