Certain forms of inflammatory arthritis involve autoreactive immunologic processes (1-3), which are accompanied by an increase in the pivotal inflammatory cytokine, TNF-alpha. Our laboratory has shown that a diet rich in glycine can prevent increases in TNFalpha in several other models of inflammatory tissue injury. Thus, it is hypothesized that glycine will prevent arthritis by decreasing TNFalpha production by macrophages. In studies of liver injury, glycine blunted the LPS-induced increased in calcium and cytokines in Kupffer cells, a phenomenon which was blocked by strychnine and was dependent on chloride, just like the glycine-gated chloride channel in the CNS. In a initial series of proposed experiments, 4 groups of Lewis female rats (10 each) will be compared in a model of arthritis using bacterial group A steptococcal peptidoglycan- polysaccharide (PG-PS) (control, glycine 5%, PG-PS and glycine + PG-PS). In the acute phase of this model, inflammation peaks in 1-2 days after the i.a. injection of PG-PS and resolves in 3 weeks. Subsequent i.v. injections of PG-PS causes 100% reactivation of chronic inflammation. Food consumption, body weight, the arthritis index and ankle thickness will be monitored at 1-3 day intervals for 6 weeks. When maximal swelling occurs, rats will be sacrificed and joint tissue will be fixed for histological evaluation. We expect dietary glycine to minimize or prevent arthritis. Second, the dose-response for glycine in PG-PS induced arthritis will be determined. Dietary glycine will be varied (0% to 5%) and the parameters described above will be evaluated. In all groups, blood samples will be collected and serum glycine levels determined. We expect glycine to be protective in experimental arthritis in the 0.5-1.0 Mm range. Third, the ability of glycine to reverse arthritis will be evaluated. To test this unique idea, glycine or control diet will be initiated at the peak of inflammation and the time course of recovery will be evaluated. Fourth, to evaluate mechanism, splenic macrophages and blood lymphocytes will be isolated at the peaks of inflammation in the 4 groups detailed above. Changes in intracellular calcium, membrane potential and key cytokines (TNFalpha, IFNgamma, IL-2, IL-4 and IL-10) will be measured as well as the response to added PG-PS. The transcription factor NFkappaB will also be determined as it is pivotal in TNFalpha production. We expect that glycine will prevent arthritis b activating a strychnine sensitive glycine-gated chloride channel in macrophages and/or T-lymphocytes making them less responsive to inflammatory agonists. Collectively, we expect these studies to demonstrate that dietary glycine will block cytokine release, reduce inflammation and prevent arthritis. This work is timely and practical and will lead to simple, dietary interventions to prevent arthritis.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Chapel Hill
United States
Zip Code
Corsi, Michela; Alvarez, Carolina; Callahan, Leigh F et al. (2018) Contributions of symptomatic osteoarthritis and physical function to incident cardiovascular disease. BMC Musculoskelet Disord 19:393
Longobardi, L; Jordan, J M; Shi, X A et al. (2018) Associations between the chemokine biomarker CCL2 and knee osteoarthritis outcomes: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage 26:1257-1261
Raveendran, R; Stiller, J L; Alvarez, C et al. (2018) Population-based prevalence of multiple radiographically-defined hip morphologies: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage 26:54-61
Goode, A P; Nelson, A E; Kraus, V B et al. (2017) Biomarkers reflect differences in osteoarthritis phenotypes of the lumbar spine: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage 25:1672-1679
Barbour, Kamil E; Murphy, Louise B; Helmick, Charles G et al. (2017) Bone Mineral Density and the Risk of Hip and Knee Osteoarthritis: The Johnston County Osteoarthritis Project. Arthritis Care Res (Hoboken) 69:1863-1870
Liu, Youfang; Yau, Michelle S; Yerges-Armstrong, Laura M et al. (2017) Genetic Determinants of Radiographic Knee Osteoarthritis in African Americans. J Rheumatol 44:1652-1658
Yau, Michelle S; Yerges-Armstrong, Laura M; Liu, Youfang et al. (2017) Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians. Arthritis Rheumatol 69:343-351
Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang et al. (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:80
Qin, Jin; Barbour, Kamil E; Murphy, Louise B et al. (2017) Lifetime Risk of Symptomatic Hand Osteoarthritis: The Johnston County Osteoarthritis Project. Arthritis Rheumatol 69:1204-1212
An, H; Marron, J S; Schwartz, T A et al. (2016) Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women. Osteoarthritis Cartilage 24:640-6

Showing the most recent 10 out of 162 publications