A central role for reactive oxygen species (ROS) in the pathogenesis of temporomandibular joint disorders: All roads lead to ROS
Abstract
Temporomandibular joint disease (TMD) is a musculoskeletal pain disorder occurring at the temporomandibular joint (TMJ), the interface of the skull’s temporal bone and the mandible1. This literature review examines the anatomy, epidemiology, biochemistry and cellular biology of TMD in order to frame underlying biochemical and cellular events within the human context of the disease. This review identifies several key elements pertaining to TMD pathogenesis, including mechanical stress-induced hypoxia-reperfusion, disruption of mitochondrial function, arachidonic acid catabolism (through prostaglandins and leukotrienes), cartilage degradation, bone resorption, and breakdown of joint lubrication. Based on a thorough analysis of established correlations and causations we propose an overarching mechanism that provides a holistic representation of TMD, something noticeably absent in the literature to-date. This mechanism clearly highlights the central role of reactive oxygen species (ROS) in the pathogenesis of TMD, a conclusion holding significant implications for both treatment and our understanding of the disease.
References
Nitzan DW. The process of lubrication impairment and its involvement in temporomandibular joint disc displacement: A theoretical concept. Journal of Oral and Maxillofacial Surgery. 2001;59(1): 36-45.
Drake, R., Tibbitts, R., & Horn, A. (2015). Gray's anatomy for students. Philadelphia: Churchill Livingstone, Elsevier.
Kawai Y, Kubota E. Oxidative stress and temporomandibular joint disorders. Japanese Dental Science Review. 2008;44(2):145-50.
Matsuo W, Kimura H, Komatsu K, Kobayashi W, Sakuraba Y, Suzuki M. The scavenging effects of TMJ synovial fluids on active oxygen generation. Journal of Japanese Society for TMJ. 1993;5: 347-55.
Milam SB, Zardeneta G, Schmitz JP. Oxidative stress and degenerative temporomandibular joint disease: A proposed hypothesis. Journal of Oral and Maxillofacial Surgery. 1998;56(2): 214-223.
Tanne K. Degenerative changes of articular cartilage in association with mechanical stimuli. Japanese Dental Science Review. 2008;44(1): 38-47.
Zardeneta G, Milam SB, Schmitz JP. Iron-dependent generation of free radicals: plausible mechanisms in the progressive deterioration of the temporomandibular joint. Journal of oral and maxillofacial surgery. 2000;58(3): 302-308.
Kawai Y, Kubota E, Okabe E. Reactive oxygen species participation in experimentally induced arthritis of the temporomandibular joint in rats. Journal of Dental Research. 2000;79(7):1489-1495.
Nitzan, Dorrit W. Intraarticular pressure in the functioning human temporomandibular joint and its alteration by uniform elevation of the occlusal plane. Journal of Oral and Maxillofacial Surgery. 1994;52(7): 671-679.
Jaeschke, H., & Mitchell, J. R. Mitochondria and xanthine oxidase both generate reactive oxygen species in isolated perfused rat liver after hypoxic injury. Biochemical and biophysical research communications. 1989;160(1): 140-147.
Semenza GL. Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2011;1813(7): 1263-1268.
Lenaz G. The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB life. 2001;52(3‐5): 159-164.
Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT. Reactive Oxygen Species Generated at Mitochondrial Complex III Stabilize Hypoxia-inducible Factor-1α during Hypoxia A MECHANISM OF O2 SENSING. Journal of Biological Chemistry. 2000;275(33): 25130-25138.
Kayyali US, Donaldson C, Huang H, Abdelnour R, Hassoun PM. Phosphorylation of xanthine dehydrogenase/oxidase in hypoxia. Journal of Biological Chemistry. 2001;276(17): 14359-14365.
Poss WB, Huecksteadt TP, Panus PC, Freeman BA, Hoidal JR. Regulation of xanthine dehydrogenase and xanthine oxidase activity by hypoxia. American Journal of Physiology-Lung Cellular and Molecular Physiology. 1996;270(6): L941-L946.
Fridovich I. Superoxide radical: an endogenous toxicant. Annual Review of Pharmacology and Toxicology. 1983;23(1): 239-257.
Lee MC, Kawai Y, Shoji H, Yoshino F, Miyazaki H, Kato H, Suga M, Kubota E. Evidence of reactive oxygen species generation in synovial fluid from patients with temporomandibular disease by electron spin resonance spectroscopy. Redox report. 2004;9(6): 331-336.
Tomida M, Ishimaru JI, Murayama K, Kajimoto T, Kurachi M, Era S, Shibata T. Intra-articular oxidative state correlated with the pathogenesis of disorders of the temporomandibular joint. British Journal of Oral and Maxillofacial Surgery. 2004;42(5): 405-409.
Nathan C, Cunningham-Bussel A. Beyond oxidative stress: an immunologist's guide to reactive oxygen species. Nature Reviews Immunology. 2013;13(5): 349-361.
Funk, C. (2001). Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology. Science. 2001; 294(5548): 1871-1875.
Kidd B. Mechanisms of inflammatory pain. British Journal of Anaesthesia. 2001;87(1): 3-11.
Feng LI, Xia YI, Garcia GE, Hwang D, Wilson CB. Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide. Journal of Clinical Investigation. 1995;95(4): 1669-1675.
Tabatabaie T, Vasquez-Weldon A, Moore DR, Kotake Y. Free Radicals and the pathogenesis of type 1 diabetes β-cell cytokine-mediated free radical generation via cyclooxygenase-2. Diabetes. 2003;52(8): 1994-1999.
Kerins C, Carlson D, McIntosh J, Bellinger L. A role for cyclooxygenase II inhibitors in modulating temporomandibular joint inflammation from a meal pattern analysis perspective. Journal of oral and maxillofacial surgery. 2004;62(8): 989-995.
Martínez-Revelles S, Avendaño MS, García-Redondo AB, Álvarez Y, Aguado A, Pérez-Girón JV, García-Redondo L, Esteban V, Redondo JM, Alonso MJ, Briones AM. Reciprocal relationship between reactive oxygen species and cyclooxygenase-2 and vascular dysfunction in hypertension. Antioxidants & redox signaling. 2013;18(1): 51-65.
Hernanz, R., Briones, A., Salaices, M., & Alonso, M. (2014). New roles for old pathways? A circuitous relationship between reactive oxygen species and cyclo-oxygenase in hypertension. Clinical Science. 2014;126(2): 111-121.
Paravicini, T., & Touyz, R. NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities. Diabetes Care. 2008;31(S2): S170-S180.
Burke, J., & Dennis, E. (2008). Phospholipase A2 Biochemistry. Cardiovascular Drugs and Therapy. 2009;23(1): 49-59.
Cocco, T., Di, M., Papa, P., & Lorusso, M. Arachidonic acid interaction with the mitochondrial electron transport chain promotes reactive oxygen species generation. Free Radical Biology And Medicine.1999;27(1-2): 51-59.
Woo, C., You, H., Cho, S., Eom, Y., Chun, J., Yoo, Y., & Kim, J. Leukotriene B4 Stimulates Rac-ERK Cascade to Generate Reactive Oxygen Species That Mediates Chemotaxis. Journal Of Biological Chemistry. 2001; 277(10): 8572-8578.
Kuroda S, Tanimoto K, Izawa T, Fujihara S, Koolstra JH, Tanaka E. Biomechanical and biochemical characteristics of the mandibular condylar cartilage. Osteoarthritis and Cartilage. 2009;17(11): 1408-1415.
Wang L, Lazebnik M, Detamore MS. Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application. Osteoarthritis and Cartilage. 2009;17(3): 346-353.
Klinge RF. The structure of the mandibular condyle in the monkey (Macaca mulatta). Micron. 1996 Oct;27(5): 381-387.
Singh M, Detamore MS. Tensile Properties of the Mandibular Condylar Cartilage. Journal of Biomechanical Engineering. 2008;130(1): 011009-1 – 011009-7.
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Molecular and Cellular Biology. 1996;16(9): 4604-4613.
Lin C, McGough R, Aswad B, Block JA, Terek R. Hypoxia induces HIF-1α and VEGF expression in chondrosarcoma cells and chondrocytes. Journal of Orthopaedic Research. 2004;22(6): 1175-1181.
Kim C-H, Cho Y-S, Chun Y-S, Park J-W, Kim M-S. Early Expression of Myocardial HIF-1α in Response to Mechanical Stresses Regulation by Stretch-Activated Channels and the Phosphatidylinositol 3-Kinase Signaling Pathway. Circulation Research. 2002;90(2): E25-E33.
Chun Y-S, Kim M-S, Park J-W. Oxygen-dependent and -independent regulation of HIF-1alpha. Journal of Korean Medical Science. 2002;17(5): 581-588.
Pufe T, Lemke A, Kurz B, Petersen W, Tillmann B, Grodzinsky AJ, Mentlein R. Mechanical Overload Induces VEGF in Cartilage Discs via Hypoxia-Inducible Factor. The American Journal of Pathology. 2004;164(1): 185-192.
Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovascular Research. 2006;69(3): 562-573.
Honda K, Ohno S, Tanimoto K, Ijuin C, Tanaka N, Doi T, Kato Y, Tanne K. The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes. European Journal of Cellular Biology. 2000;79(9): 601-609.
Wong M, Siegrist M, Goodwin K. Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes. Bone. 2003;33(4): 685-693.
Tanaka E, Aoyama J, Miyauchi M, Takata T, Hanaoka K, Iwabe T, Tanne K. Vascular endothelial growth factor plays an important autocrine/paracrine role in the progression of osteoarthritis. Histochemistry and Cell Biology. 2005;123(3): 275-281.
Engsig MT, Chen Q-J, Vu TH, Pedersen A-C, Therkidsen B, Lund LR, Henriksen K, Lenhard T, Foged NT, Werb Z, Delaissé JM. Matrix Metalloproteinase 9 and Vascular Endothelial Growth Factor Are Essential for Osteoclast Recruitment into Developing Long Bones. Journal of Cellular Biology. 2000;151(4): 879-890.
Niida S, Kaku M, Amano H, Yoshida H, Kataoka H, Nishikawa S, Kodama H. Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone Resorption. The Journal of Experimental Medicine. 1999;190(2): 293-298.
Das S, Banquy X, Zappone B, Greene GW, Jay GD, Israelachvili JN. Synergistic interactions between grafted hyaluronic acid and lubricin provide enhanced wear protection and lubrication. Biomacromolecules. 2013;14(5): 1669-1677.
Hills BA. Oligolamellar lubrication of joints by surface active phospholipid. The Journal of rheumatology. 1989;16(1): 82-91.
Schwarz IM, Hills BA. Surface-active phospholipid as the lubricating component of lubricin. Rheumatology. 1998;37(1): 21-26.
Nitzan DW, Nitzan U, Dan P, Yedgar S. The role of hyaluronic acid in protecting surface‐active phospholipids from lysis by exogenous phospholipase A2. Rheumatology. 2001;40(3): 336-340.
Swann DA, Radin EL, Nazimiec MI, Weisser PA, Curran NA, Lewinnek G. Role of hyaluronic acid in joint lubrication. Annals of the rheumatic diseases. 1974;33(4): 318-326.
Linn FC. Lubrication of animal joints: II the mechanism. Journal of biomechanics. 1968;1(3): 193-205.
Necas J, Bartosikova L, Brauner P, Kolar J. Hyaluronic acid (hyaluronan): a review. Veterinarni medicina. 2008;53(8): 397-411.
Campo GM, Avenoso A, Campo S, D'Ascola A, Traina P, Calatroni A. Effect of cytokines on hyaluronan synthase activity and response to oxidative stress by fibroblasts. British Journal of Biomedical Science. 2009;66(1): 28-36.
Li J, Long X, Ke J, Meng QG, Lee WC, Doocey JM, Zhu F. Regulation of HAS expression in human synovial lining cells of TMJ by IL-1β. Archives of oral biology. 2008;53(1): 60-65.
Tanimoto K, Ohno S, Fujimoto K, Honda K, Ijuin C, Tanaka N, Doi T, Nakahara M, Tanne K. Proinflammatory cytokines regulate the gene expression of hyaluronic acid synthetase in cultured rabbit synovial membrane cells. Connective tissue research. 2001;42(3): 187-195.
Tanimoto K, Suzuki A, Ohno S, Honda K, Tanaka N, Doi T et al. Effects of TGF-β on Hyaluronan Anabolism in Fibroblasts Derived from the Synovial Membrane of the Rabbit Temporomandibular Joint. Journal of Dental Research. 2004;83(1): 40-44.
Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M et al. Three Isoforms of Mammalian Hyaluronan Synthases Have Distinct Enzymatic Properties. Journal of Biological Chemistry. 1999;274(35): 25085-25092.
Presti D, Scott JE. Hyaluronan‐mediated protective effect against cell damage caused by enzymatically produced hydroxyl (OH·) radicals is dependent on hyaluronan molecular mass. Cell biochemistry and function. 1994;12(4): 281-288.
Moseley R, Leaver M, Walker M, Waddington RJ, Parsons D, Chen WY, Embery G. Comparison of the antioxidant properties of HYAFF®-11p75, AQUACEL® and hyaluronan towards reactive oxygen species in vitro. Biomaterials. 2002;23(10): 2255-2264.
Roberts CR, Roughley PJ, Mort JS. Degradation of human proteoglycan aggregate induced by hydrogen peroxide. The Biochemical Journal. 1989;259(3): 805-811.
Wang CT, Lin YT, Chiang BL, Lin YH, Hou SM. High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis. Osteoarthritis and Cartilage. 2006;14(12): 1237-1247.
Koyama E, Saunders C, Salhab I, Decker RS, Chen I, Um H, Pacifici M, Nah HD. Lubricin is required for the structural integrity and post-natal maintenance of TMJ. Journal of dental research. 2014;93(7): 663-670.
Waddington RJ, Moseley R, Embery G. Periodontal Disease Mechanisms: Reactive oxygen species: a potential role in the pathogenesis of periodontal diseases. Oral diseases. 2000;6(3): 138-151.
Henrotin YE, Bruckner P, Pujol JP. The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis and Cartilage. 2003;11(10): 747-755.
Lemos GA, Rissi R, Pimentel ER, Palomari ET. Effects of high molecular weight hyaluronic acid on induced arthritis of the temporomandibular joint in rats. Acta histochemica. 2015;117(6): 566-575.
Manfredini D, Piccotti F, Guarda-Nardini L. Hyaluronic acid in the treatment of TMJ disorders: a systematic review of the literature. Cranio: The Journal of Craniomandibular Practice. 2010;28(3): 166-176.