Bitter Taste Receptor as a Therapeutic Target in Orthopaedic Disorders

• Published in: Drug design, development and therapy Vol. 15; pp. 895 - 903
• Main Authors: Cheng, Weyland, Yao, Manye, Liu, Fangna
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Anti-Inflammatory Agents - pharmacology; Bacteria; Biofilms; Biomedical materials; Bitter taste; Bone growth; bone inflammation; Bone resorption; Calcium; Calcium (intracellular); Calcium (reticular); calcium signaling; Cell activation; Disorders; drug target; Endoplasmic reticulum; Genotype & phenotype; Gram-negative bacteria; Gram-positive bacteria; Granulocytes; Health aspects; Histamine; Homeostasis; Humans; Hypothesis; Immune system; Immunotherapy; Inflammation; Innate immunity; Inositol trisphosphate; Intracellular; Kinases; Molecular Structure; Musculoskeletal Diseases - drug therapy; Musculoskeletal Diseases - immunology; Nitric oxide; Orthopedics; Osteitis - drug therapy; Osteitis - immunology; osteoblasts; Osteoclasts; Osteocytes; Osteogenesis; Phospholipase C; Proteins; Receptors; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - immunology; tas2r; Taste; Taste receptors; Tumor necrosis factor-TNF; TAS2R; bone inflammation; osteoblasts; drug target; calcium signaling
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S289614

Non-gustatory, extraoral bitter taste receptors (T2Rs) are G-protein coupled receptors that are expressed throughout the body and have various functional responses when stimulated by bitter agonists. Presently, T2Rs have been found to be expressed in osteoclasts and osteocytes where osteoclasts were capable of detecting bacterial quorum-sensing molecules through the T2R38 isoform. In the innate immune system, stimulating T2Rs induces anti-inflammatory and anti-pathogenic effects through the phospholipase C/inositol triphosphate pathway, which leads to intracellular calcium release from the endoplasmic reticulum. The immune cells with functional responses to T2R activation also play a role in bone inflammation and orthopaedic disorders. Furthermore, increasing intracellular calcium levels in bone cells through T2R activation can potentially influence bone formation and resorption. With recent studies finding T2R expression in bone cells, we examine the potential of targeting this receptor to treat bone inflammation and to promote bone anabolism.