PH.D. Western University
MD Western University
Office: Dental Sciences Building, Room 0073
p. 519.661.2111 x.83768
See Publications by Tom Appleton on PubMed
Dr. Appleton received his PhD in Physiology in 2007 working on osteoarthritis (OA) in the laboratory of Dr. Frank Beier on pathophysiological mechanisms of cartilage damage in animal models of post-traumatic OA. He continued to work in the OA research field while completing his medical degree, residency in internal medicine and fellowship in Rheumatology at Western University.
Using genetic and molecular techniques, his work has identified a signaling axis involving transforming growth factor alpha (TGFa) and chemokine (C-C motif) ligand 2 (CCL2) in early post-traumatic OA. More recently, he has demonstrated the efficacy of targeting this signaling axis in pre-clinical studies. Dr. Appleton’s current research interests include cell-mediated tissue damage, synovitis and inflammatory features of OA, and discovering the pathophysiology of different clinical OA phenotypes.
By establishing a translational biology research program in early OA, which includes multidisciplinary collaborative projects with members of the Western University Bone and Joint Institute and members of the musculoskeletal research community in Canada and internationally, Dr. Appleton is investigating the mechanisms of osteoarthritis disease development and progression to identify new therapeutic targets for disease modifying OA therapies. The research program in osteoarthritis includes a prospective, longitudinal patient cohort of patients with early OA of various phenotypes.
Dr. Appleton joined the Division of Rheumatology in 2016 as a Clinician Scientist and provides clinical service to patients with inflammatory rheumatologic disorders in addition to running the translational early OA research program. His cross appointment in the Department of Physiology & Pharmacology in 2017 facilitates the discovery aspect of the research program in the laboratory utilizing multiple molecular biology techniques. The main focus of the lab is studying the molecular interplay between synovium and articular cartilage and the inflammatory mediators that drive joint damage and dysfunction in early OA.
Appleton CT, Hawker GA, Hill CL, Pope JE. 'Weighing in' on Framingham OA: Measuring biomechanical and metabolic contributions to osteoarthritis. Arthritis Rheumatol. 2017 Mar 7. doi: 10.1002/art.40089. [Epub ahead of print] PubMed PMID: 28267901.
Appleton CT. What's pain (sensitization) got to do with it? Microgliosis may be a treatment target in osteoarthritis-related pain sensitization. Osteoarthritis Cartilage. 2017 Feb 20. pii: S1063-4584(17)30865-8. doi: 10.1016/j.joca.2017.02.798. [Epub ahead of print] PubMed PMID: 28223124.
Appleton CT, Usmani SE, Pest MA, Pitelka V, Mort JS, Beier F. Reduction in disease progression by inhibition of transforming growth factor α-CCL2 signaling in experimental posttraumatic osteoarthritis. Arthritis Rheumatol. 2015 Oct;67(10):2691-701. doi: 10.1002/art.39255. PubMed PMID: 26138996.
Lai Y, Bai X, Zhao Y, Tian Q, Liu B, Lin EA, Chen Y, Lee B, Appleton CT, Beier F, Yu XP, Liu CJ. ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis. Ann Rheum Dis. 2014 Aug;73(8):1575-84. doi: 10.1136/annrheumdis-2013-203561. PubMed PMID: 23928557; PubMed Central PMCID: PMC4418017.
Usmani SE, Appleton CT, Beier F. Transforming growth factor-alpha induces endothelin receptor A expression in osteoarthritis. J Orthop Res. 2012 Sep;30(9):1391-7. doi: 10.1002/jor.22099. PubMed PMID: 22407503.
Appleton CT, Usmani SE, Mort JS, Beier F. Rho/ROCK and MEK/ERK activation by transforming growth factor-alpha induces articular cartilage degradation. Lab Invest. 2010 Jan;90(1):20-30. doi: 10.1038/labinvest.2009.111. PubMed PMID: 19823173.
Cecil DL, Appleton CT, Polewski MD, Mort JS, Schmidt AM, Bendele A, Beier F, Terkeltaub R. The pattern recognition receptor CD36 is a chondrocyte hypertrophy marker associated with suppression of catabolic responses and promotion of repair responses to inflammatory stimuli. J Immunol. 2009 Apr 15;182(8):5024-31. doi: 10.4049/jimmunol.0803603. PubMed PMID: 19342682; PubMed Central PMCID: PMC2698125.
Attur MG, Palmer GD, Al-Mussawir HE, Dave M, Teixeira CC, Rifkin DB, Appleton CT, Beier F, Abramson SB. F-spondin, a neuroregulatory protein, is up-regulated in osteoarthritis and regulates cartilage metabolism via TGF-beta activation. FASEB J. 2009 Jan;23(1):79-89. doi: 10.1096/fj.08-114363. Erratum in: FASEB J. 2009 Aug;23(8):2790. PubMed PMID: 18780763; PubMed Central PMCID: PMC2626615.
Appleton CT, Usmani SE, Bernier SM, Aigner T, Beier F. Transforming growth factor alpha suppression of articular chondrocyte phenotype and Sox9 expression in a rat model of osteoarthritis. Arthritis Rheum. 2007 Nov;56(11):3693-705. PubMed PMID: 17968906.
McErlain DD, Appleton CT, Litchfield RB, Pitelka V, Henry JL, Bernier SM, Beier F, Holdsworth DW. Study of subchondral bone adaptations in a rodent surgical model of OA using in vivo micro-computed tomography. Osteoarthritis Cartilage. 2008 Apr;16(4):458-69. PubMed PMID: 17900933; PubMed Central PMCID: PMC5130342.
Appleton CT, McErlain DD, Henry JL, Holdsworth DW, Beier F. Molecular and histological analysis of a new rat model of experimental knee osteoarthritis. Ann N Y Acad Sci. 2007 Nov;1117:165-74. PubMed PMID: 17646269.
Appleton CT, Pitelka V, Henry J, Beier F. Global analyses of gene expression in early experimental osteoarthritis. Arthritis Rheum. 2007 Jun;56(6):1854-68. PubMed PMID: 17530714.
Appleton CT, McErlain DD, Pitelka V, Schwartz N, Bernier SM, Henry JL, Holdsworth DW, Beier F. Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis. Arthritis Res Ther. 2007;9(1):R13. Erratum in: Arthritis Res Ther. 2008;10(5):407. PubMed PMID: 17284317; PubMed Central PMCID: PMC1860072.