Bitter Taste Receptor as a Therapeutic Target in Orthopaedic Disorders

References

• SchiothHB, FredrikssonR. The GRAFS classification system of G-protein coupled receptors in comparative perspective. Gen Comp Endocrinol. 2005;142(1–2):94–101. doi:10.1016/j.ygcen.2004.12.01815862553
   PubMed Web of Science ®Google Scholar
• MargolskeeRF. Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem. 2002;277(1):1–4. doi:10.1074/jbc.R10005420011696554
   PubMed Web of Science ®Google Scholar
• ChaudhariN, RoperSD. The cell biology of taste. J Cell Biol. 2010;190(3):285–296. doi:10.1083/jcb.20100314420696704
   PubMed Web of Science ®Google Scholar
• ClappTR, StoneLM, MargolskeeRF, KinnamonSC. Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction. BMC Neurosci. 2001;2:6. doi:10.1186/1471-2202-2-611346454
   PubMed Web of Science ®Google Scholar
• LindemannB. Chemoreception: tasting the sweet and the bitter. Curr Biol. 1996;6(10):1234–1237. doi:10.1016/S0960-9822(96)00704-X8939555
   PubMed Web of Science ®Google Scholar
• KinnamonSC. Taste receptor signalling - from tongues to lungs. Acta Physiol (Oxf). 2012;204(2):158–168. doi:10.1111/j.1748-1716.2011.02308.x21481196
   PubMed Web of Science ®Google Scholar
• JaggupilliA, SinghN, UpadhyayaJ, et al. Analysis of the expression of human bitter taste receptors in extraoral tissues. Mol Cell Biochem. 2017;426(1–2):137–147. doi:10.1007/s11010-016-2902-z28012014
   PubMed Web of Science ®Google Scholar
• BloxhamCJ, FosterSR, ThomasWG. A bitter taste in your heart. Front Physiol. 2020;11:431. doi:10.3389/fphys.2020.0043132457649
   PubMed Web of Science ®Google Scholar
• DeshpandeDA, WangWC, McIlmoyleEL, et al. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med. 2010;16(11):1299–1304. doi:10.1038/nm.223720972434
   PubMed Web of Science ®Google Scholar
• DotsonCD, ZhangL, XuH, et al. Bitter taste receptors influence glucose homeostasis. PLoS One. 2008;3(12):e3974. doi:10.1371/journal.pone.000397419092995
   PubMed Web of Science ®Google Scholar
• LeeRJ, XiongG, KofonowJM, et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest. 2012;122(11):4145–4159. doi:10.1172/JCI6424023041624
   PubMed Web of Science ®Google Scholar
• Orsmark-PietrasC, JamesA, KonradsenJR, et al. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur Respir J. 2013;42(1):65–78. doi:10.1183/09031936.0007771223222870
   PubMed Web of Science ®Google Scholar
• ShahAS, Ben-ShaharY, MoningerTO, KlineJN, WelshMJ. Motile cilia of human airway epithelia are chemosensory. Science. 2009;325(5944):1131–1134. doi:10.1126/science.117386919628819
   PubMed Web of Science ®Google Scholar
• LeeRJ, CohenNA. Taste receptors in innate immunity. Cell Mol Life Sci. 2015;72(2):217–236.25323130
   PubMed Web of Science ®Google Scholar
• GaidaMM, DapuntU, HanschGM, BjarnsholtT. Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells. Pathog Dis. 2016;74(3):ftw004. doi:10.1093/femspd/ftw00426782143
   PubMed Web of Science ®Google Scholar
• LundTC, KobsAJ, KramerA, et al. Bone marrow stromal and vascular smooth muscle cells have chemosensory capacity via bitter taste receptor expression. PLoS One. 2013;8(3):e58945. doi:10.1371/journal.pone.005894523520545
   PubMed Web of Science ®Google Scholar
• WangY, ZajacAL, LeiW, et al. Metal ions activate the human taste receptor TAS2R7. Chem Senses. 2019;44(5):339–347. doi:10.1093/chemse/bjz02431066447
   PubMed Web of Science ®Google Scholar
• ZamoraR, VodovotzY, BilliarTR. Inducible nitric oxide synthase and inflammatory diseases. Mol Med. 2000;6(5):347–373.10952018
   PubMed Web of Science ®Google Scholar
• FreundJR, MansfieldCJ, DoghramjiLJ, et al. Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling. J Biol Chem. 2018;293(25):9824–9840. doi:10.1074/jbc.RA117.00100529748385
   PubMed Web of Science ®Google Scholar
• MaurerS, WabnitzGH, KahleNA, et al. Tasting pseudomonas aeruginosa biofilms: human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone. Front Immunol. 2015;6:369. doi:10.3389/fimmu.2015.0036926257736
   PubMed Web of Science ®Google Scholar
• CareyRM, WorkmanAD, YanCH, et al. Sinonasal T2R-mediated nitric oxide production in response to Bacillus cereus. Am J Rhinol Allergy. 2017;31(4):211–215. doi:10.2500/ajra.2017.31.445328716170
   PubMed Web of Science ®Google Scholar
• CareyRM, WorkmanAD, ChenB, et al. Staphylococcus aureus triggers nitric oxide production in human upper airway epithelium. Int Forum Allergy Rhinol. 2015;5(9):808–813. doi:10.1002/alr.2156826097237
   PubMed Web of Science ®Google Scholar
• CareyRM, ChenB, AdappaND, et al. Human upper airway epithelium produces nitric oxide in response to Staphylococcus epidermidis. Int Forum Allergy Rhinol. 2016;6(12):1238–1244. doi:10.1002/alr.2183727509402
   PubMed Web of Science ®Google Scholar
• GopallawaI, FreundJR, LeeRJ. Bitter taste receptors stimulate phagocytosis in human macrophages through calcium, nitric oxide, and cyclic-GMP signaling. Cell Mol Life Sci. 2020;78(1):271–286. doi:10.1007/s00018-020-03494-y32172302
   PubMed Web of Science ®Google Scholar
• TranHTT, HerzC, RufP, StetterR, LamyE. Human T2R38 bitter taste receptor expression in resting and activated lymphocytes. Front Immunol. 2018;9:2949. doi:10.3389/fimmu.2018.0294930619309
   PubMed Web of Science ®Google Scholar
• EkoffM, ChoiJH, JamesA, DahlenB, NilssonG, DahlenSE. Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation. J Allergy Clin Immunol. 2014;134(2):475–478. doi:10.1016/j.jaci.2014.02.02924755408
   PubMed Web of Science ®Google Scholar
• DrewnowskiA, HendersonSA, ShoreAB. Genetic sensitivity to 6-n-propylthiouracil (PROP) and hedonic responses to bitter and sweet tastes. Chem Senses. 1997;22(1):27–37. doi:10.1093/chemse/22.1.279056083
   PubMed Web of Science ®Google Scholar
• BartoshukLM, DuffyVB, MillerIJ. PTC/PROP tasting: anatomy, psychophysics, and sex effects. Physiol Behav. 1994;56(6):1165–1171. doi:10.1016/0031-9384(94)90361-17878086
   PubMed Web of Science ®Google Scholar
• Whissell-BuechyD, WillsC. Male and female correlations for taster (P.T.C.) phenotypes and rate of adolescent development. Ann Hum Biol. 1989;16(2):131–146. doi:10.1080/030144687000069822729890
   PubMed Web of Science ®Google Scholar
• KimUK, JorgensonE, CoonH, LeppertM, RischN, DraynaD. Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science. 2003;299(5610):1221–1225. doi:10.1126/science.108019012595690
   PubMed Web of Science ®Google Scholar
• Whissell-BuechyD. Effects of age and sex on taste sensitivity to phenylthiocarbamide (PTC) in the Berkeley guidance sample. Chem Senses. 1990;15(1):39–57. doi:10.1093/chemse/15.1.39
   Web of Science ®Google Scholar
• AdappaND, HowlandTJ, PalmerJN, et al. Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention. Int Forum Allergy Rhinol. 2013;3(3):184–187. doi:10.1002/alr.2114023322450
   PubMed Web of Science ®Google Scholar
• Mfuna EndamL, Filali-MouhimA, BoisvertP, BouletLP, BosseY, DesrosiersM. Genetic variations in taste receptors are associated with chronic rhinosinusitis: a replication study. Int Forum Allergy Rhinol. 2014;4(3):200–206. doi:10.1002/alr.2127524415641
   PubMed Web of Science ®Google Scholar
• AdappaND, ZhangZ, PalmerJN, et al. The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery. Int Forum Allergy Rhinol. 2014;4(1):3–7. doi:10.1002/alr.2125324302675
   PubMed Web of Science ®Google Scholar
• AdappaND, FarquharD, PalmerJN, et al. TAS2R38 genotype predicts surgical outcome in nonpolypoid chronic rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(1):25–33. doi:10.1002/alr.2166626562612
   PubMed Web of Science ®Google Scholar
• AdappaND, TruesdaleCM, WorkmanAD, et al. Correlation of T2R38 taste phenotype and in vitro biofilm formation from nonpolypoid chronic rhinosinusitis patients. Int Forum Allergy Rhinol. 2016;6(8):783–791. doi:10.1002/alr.2180327309535
   PubMed Web of Science ®Google Scholar
• RomDI, ChristensenJM, AlvaradoR, SacksR, HarveyRJ. The impact of bitter taste receptor genetics on culturable bacteria in chronic rhinosinusitis. Rhinology. 2017;55(1):90–94. doi:10.4193/Rhin16.18128214914
   PubMed Web of Science ®Google Scholar
• ZayzafoonM. Calcium/calmodulin signaling controls osteoblast growth and differentiation. J Cell Biochem. 2006;97(1):56–70. doi:10.1002/jcb.2067516229015
   PubMed Web of Science ®Google Scholar
• ThemanTA, CollinsMT. The role of the calcium-sensing receptor in bone biology and pathophysiology. Curr Pharm Biotechnol. 2009;10(3):289–301. doi:10.2174/13892010978784753819355939
   PubMed Web of Science ®Google Scholar
• GoltzmanD, HendyGN. The calcium-sensing receptor in bone–mechanistic and therapeutic insights. Nat Rev Endocrinol. 2015;11(5):298–307. doi:10.1038/nrendo.2015.3025752283
   PubMed Web of Science ®Google Scholar
• FromigueO, HayE, BarbaraA, et al. Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. J Cell Mol Med. 2009;13(8B):2189–2199. doi:10.1111/j.1582-4934.2008.00673.x20141614
   PubMed Web of Science ®Google Scholar
• PiM, GarnerSC, FlanneryP, SpurneyRF, QuarlesLD. Sensing of extracellular cations in CasR-deficient osteoblasts. Evidence for a novel cation-sensing mechanism. J Biol Chem. 2000;275(5):3256–3263. doi:10.1074/jbc.275.5.325610652312
   PubMed Web of Science ®Google Scholar
• MariePJ. The calcium-sensing receptor in bone cells: a potential therapeutic target in osteoporosis. Bone. 2010;46(3):571–576. doi:10.1016/j.bone.2009.07.08219660583
   PubMed Web of Science ®Google Scholar
• TordoffMG. Calcium: taste, intake, and appetite. Physiol Rev. 2001;81(4):1567–1597. doi:10.1152/physrev.2001.81.4.156711581497
   PubMed Web of Science ®Google Scholar
• HwangSY, PutneyJW Jr. Calcium signaling in osteoclasts. Biochim Biophys Acta. 2011;1813(5):979–983. doi:10.1016/j.bbamcr.2010.11.00221075150
   PubMed Web of Science ®Google Scholar
• YamaguchiM, HamamotoR, UchiyamaS, IshiyamaK. Effects of flavonoid on calcium content in femoral tissue culture and parathyroid hormone-stimulated osteoclastogenesis in bone marrow culture in vitro. Mol Cell Biochem. 2007;303(1–2):83–88. doi:10.1007/s11010-007-9458-x17541507
   PubMed Web of Science ®Google Scholar
• MeyerhofW, BatramC, KuhnC, et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses. 2010;35(2):157–170. doi:10.1093/chemse/bjp09220022913
   PubMed Web of Science ®Google Scholar
• LacativaPG, FariasML. Osteoporosis and inflammation. Arq Bras Endocrinol Metabol. 2010;54(2):123–132. doi:10.1590/S0004-2730201000020000720485900
   PubMedGoogle Scholar
• Abu-AmerY, DarwechI, ClohisyJC. Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapies. Arthritis Res Ther. 2007;9(Suppl 1):S6. doi:10.1186/ar2170
   PubMed Web of Science ®Google Scholar
• RueggC. Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions. J Leukoc Biol. 2006;80(4):682–684. doi:10.1189/jlb.060639416849612
   PubMed Web of Science ®Google Scholar
• RocaH, McCauleyLK. Inflammation and skeletal metastasis. Bonekey Rep. 2015;4:706. doi:10.1038/bonekey.2015.7526131358
   PubMedGoogle Scholar
• El-JawhariJJ, JonesE, GiannoudisPV. The roles of immune cells in bone healing; what we know, do not know and future perspectives. Injury. 2016;47(11):2399–2406. doi:10.1016/j.injury.2016.10.00827809990
   PubMed Web of Science ®Google Scholar
• Van’t HofRJ, RalstonSH. Nitric oxide and bone. Immunology. 2001;103(3):255–261. doi:10.1046/j.1365-2567.2001.01261.x11454054
   PubMed Web of Science ®Google Scholar
• PilbeamC. Prostaglandins and bone. In: Handb Exp Pharmacol. Berlin, Heidelberg: Springer; 2019.
   Google Scholar
• TianXY, ZhangQ, ZhaoR, et al. Continuous PGE2 leads to net bone loss while intermittent PGE2 leads to net bone gain in lumbar vertebral bodies of adult female rats. Bone. 2008;42(5):914–920. doi:10.1016/j.bone.2007.12.22818316259
   PubMed Web of Science ®Google Scholar
• RagipogluD, DudeckA, Haffner-LuntzerM, et al. The role of mast cells in bone metabolism and bone disorders. Front Immunol. 2020;11:163. doi:10.3389/fimmu.2020.0016332117297
   PubMed Web of Science ®Google Scholar
• BradyRA, LeidJG, CalhounJH, CostertonJW, ShirtliffME. Osteomyelitis and the role of biofilms in chronic infection. FEMS Immunol Med Microbiol. 2008;52(1):13–22. doi:10.1111/j.1574-695X.2007.00357.x18081847
   PubMedGoogle Scholar
• Gomez-BarrenaE, EstebanJ, MedelF, et al. Bacterial adherence to separated modular components in joint prosthesis: a clinical study. J Orthop Res. 2012;30(10):1634–1639. doi:10.1002/jor.2211422467526
   PubMed Web of Science ®Google Scholar
• EstebanJ, Cordero-AmpueroJ. Treatment of prosthetic osteoarticular infections. Expert Opin Pharmacother. 2011;12(6):899–912. doi:10.1517/14656566.2011.54367621405943
   PubMed Web of Science ®Google Scholar
• LeeRJ, KofonowJM, RosenPL, et al. Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest. 2014;124(3):1393–1405. doi:10.1172/JCI7209424531552
   PubMed Web of Science ®Google Scholar
• VarogaD, TohidnezhadM, PaulsenF, et al. The role of human beta-defensin-2 in bone. J Anat. 2008;213(6):749–757. doi:10.1111/j.1469-7580.2008.00992.x19094191
   PubMed Web of Science ®Google Scholar
• VarogaD, WruckCJ, TohidnezhadM, et al. Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3. Histochem Cell Biol. 2009;131(2):207–218. doi:10.1007/s00418-008-0522-818925411
   PubMed Web of Science ®Google Scholar
• ZhuC, QinH, ChengT, et al. Staphylococcus aureus supernatant induces the release of mouse beta-defensin-14 from osteoblasts via the p38 MAPK and NF-kappaB pathways. Int J Mol Med. 2013;31(6):1484–1494. doi:10.3892/ijmm.2013.134623588388
   PubMed Web of Science ®Google Scholar
• ThilakarathnaSH, RupasingheHP. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients. 2013;5(9):3367–3387. doi:10.3390/nu509336723989753
   PubMed Web of Science ®Google Scholar
• Roca-FerrerJ, PujolsL, Perez-GonzalezM, et al. Superior effect of MP-AzeFlu than azelastine or fluticasone propionate alone on reducing inflammatory markers. Allergy Asthma Clin Immunol. 2018;14(1):86. doi:10.1186/s13223-018-0311-430574167
   PubMed Web of Science ®Google Scholar
• EkstedtS, Kumlien GeorenS, CardellLO. Effects of MP-AzeFlu enhanced by activation of bitter taste receptor TAS2R. Allergy Asthma Clin Immunol. 2020;16(1):45. doi:10.1186/s13223-020-00438-w32514276
   PubMed Web of Science ®Google Scholar
• DelooseE, JanssenP, CorsettiM, et al. Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers. Am J Clin Nutr. 2017;105(3):580–588. doi:10.3945/ajcn.116.13829728148502
   PubMed Web of Science ®Google Scholar
• DelooseE, CorsettiM, Van OudenhoveL, DepoortereI, TackJ. Intragastric infusion of the bitter tastant quinine suppresses hormone release and antral motility during the fasting state in healthy female volunteers. Neurogastroenterol Motil. 2018;30(1):e13171. doi:10.1111/nmo.13171
   Web of Science ®Google Scholar
• WolfleU, ElsholzFA, KerstenA, HaarhausB, MullerWE, SchemppCM. Expression and functional activity of the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes. Skin Pharmacol Physiol. 2015;28(3):137–146. doi:10.1159/00036763125573083
   PubMed Web of Science ®Google Scholar
• SchemppC, WoelfleU, Inventors; Bitter taste receptor agonists for topical use. US patent WO2013112865A12013.
   Google Scholar
• EzraA, GolombG. Administration routes and delivery systems of bisphosphonates for the treatment of bone resorption. Adv Drug Deliv Rev. 2000;42(3):175–195. doi:10.1016/S0169-409X(00)00061-210963835
   PubMed Web of Science ®Google Scholar
• FordCA, CassatJE. Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis. Expert Rev Anti Infect Ther. 2017;15(9):851–860. doi:10.1080/14787210.2017.137219228837368
   PubMed Web of Science ®Google Scholar
• CarboneEJ, RajpuraK, AllenBN, ChengE, UleryBD, LoKW. Osteotropic nanoscale drug delivery systems based on small molecule bone-targeting moieties. Nanomedicine. 2017;13(1):37–47. doi:10.1016/j.nano.2016.08.01527562211
   PubMed Web of Science ®Google Scholar