Abstract
Osteoarthritis (OA), a chronic joint disease, is characterized by cartilage surface erosion, subchondral bone rebuilding, and formation of osteophytes. To date, the nosogenesis and underlying mechanisms of OA have not yet been elucidated. However, it is widely accepted that TNF-α is a crucial cytokine in the development of OA. Glycitin, a natural isoflavone extracted from legumes, affects physiological reactions and pathological responses. Recently, the anti-inflammatory effect of glycitin has been reported. However, the function of glycitin in cartilage degeneration in OA remains to be investigated. In the current study, primary murine chondrocytes were isolated and stimulated by TNF-α to evaluate the anti-inflammatory effects and protective function of glycitin in chondrocytes. In vivo, the ACLT mouse model, a frequently-used OA model, was used to further examine the therapeutic role of glycitin in cartilage degeneration and inflammation in OA. Consequently, glycitin functions were examined both in vivo and in vitro. Moreover, the underlying mechanism of action of glycitin was investigated and was found to involve the NF-κB signaling pathway. Collectively, this study suggests that glycitin can be potentially used for the treatment of joint degenerative diseases, including OA.
Similar content being viewed by others
References
Thielen, N.G.M., P.M. van der Kraan, and A.P.M. van Caam. 2019. TGFbeta/BMP signaling pathway in cartilage homeostasis. Cells 8.
Zhu, S., D. Makosa, B. Miller, and T.M. Griffin. 2019. Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis. Connective Tissue Research: 1–14.
Teirlinck, C.H., D.M.J. Dorleijn, P.K. Bos, J.B.M. Rijkels-Otters, S.M.A. Bierma-Zeinstra, and P.A.J. Luijsterburg. 2019. Prognostic factors for progression of osteoarthritis of the hip: a systematic review. Arthritis Research & Therapy 21: 192.
Lane, N.E., K. Shidara, and B.L. Wise. 2017. Osteoarthritis year in review 2016: clinical. Osteoarthritis and Cartilage 25: 209–215.
Flemming, D.J., and C.N. Gustas-French. 2017. Rapidly progressive osteoarthritis: a review of the clinical and radiologic presentation. Current Rheumatology Reports 19: 42.
Haj-Mirzaian A, Mohajer B, Guermazi A, Conaghan PG, Lima JAC, Blaha MJ, et al. 2019. Statin use and knee osteoarthritis outcome measures according to the presence of Heberden nodes: results from the osteoarthritis initiative. Radiology 190557.
Kapoor, M., J. Martel-Pelletier, D. Lajeunesse, J.P. Pelletier, and H. Fahmi. 2011. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews Rheumatology 7: 33–42.
Zhao, Y.P., B. Liu, Q.Y. Tian, J.L. Wei, B. Richbourgh, and C.J. Liu. 2015. Progranulin protects against osteoarthritis through interacting with TNF-alpha and beta-Catenin signalling. Annals of the Rheumatic Diseases 74: 2244–2253.
Hossain, F.M., Y. Hong, Y. Jin, J. Choi, and Y. Hong. 2019. Physiological and pathological role of circadian hormones in osteoarthritis: dose-dependent or time-dependent? Journal of Clinical Medicine 8.
Lai, Y., X. Bai, Y. Zhao, Q. Tian, B. Liu, E.A. Lin, Y. Chen, B. Lee, C.T. Appleton, F. Beier, X.P. Yu, and C.J. Liu. 2014. ADAMTS-7 forms a positive feedback loop with TNF-alpha in the pathogenesis of osteoarthritis. Annals of the Rheumatic Diseases 73: 1575–1584.
Zhao, Y., Y. Li, R. Qu, X. Chen, W. Wang, C. Qiu, B. Liu, X. Pan, L. Liu, K. Vasilev, J. Hayball, S. Dong, and W. Li. 2019. Cortistatin binds to TNF-alpha receptors and protects against osteoarthritis. Ebiomedicine 41: 556–570.
Mei, J., J. Sun, J. Wu, and X. Zheng. 2019. Liraglutide suppresses TNF-alpha-induced degradation of extracellular matrix in human chondrocytes: a therapeutic implication in osteoarthritis. American Journal of Translational Research 11: 4800–4808.
Martinez-Moreno, D., G. Jimenez, P. Galvez-Martin, G. Rus, and J.A. Marchal. 1865. Cartilage biomechanics: a key factor for osteoarthritis regenerative medicine. Biochimica et Biophysica Acta - Molecular Basis of Disease 2019: 1067–1075.
Hermann, J., R.W. Lipp, A. Dunzinger, C. Spreizer, G. Schaffler, H. Kvaternik, et al. 2014. Anti-TNF scintigraphy to assess TNF-alpha-associated joint inflammation in rheumatoid arthritis and osteoarthritis. Clinical and Experimental Rheumatology 32: 614.
Nelson, A.E. 2018. Osteoarthritis year in review 2017: Clinical. Osteoarthritis and Cartilage 26: 319–325.
Ibi, M. 2019. Inflammation and temporomandibular joint derangement. Biological & Pharmaceutical Bulletin 42: 538–542.
Wang, A., D.J. Leong, L. Cardoso, and H.B. Sun. 2018. Nutraceuticals and osteoarthritis pain. Pharmacology & Therapeutics 187: 167–179.
Leong, D.J., M. Choudhury, D.M. Hirsh, J.A. Hardin, N.J. Cobelli, and H.B. Sun. 2013. Nutraceuticals: potential for chondroprotection and molecular targeting of osteoarthritis. International Journal of Molecular Sciences 14: 23063–23085.
Zhang, L., J. Chen, W. Chai, M. Ni, X. Sun, and D. Tian. 2016. Glycitin regulates osteoblasts through TGF-beta or AKT signaling pathways in bone marrow stem cells. Experimental and Therapeutic Medicine 12: 3063–3067.
Chen, Y., S. Guo, K. Jiang, Y. Wang, M. Yang, and M. Guo. 2019. Glycitin alleviates lipopolysaccharide-induced acute lung injury via inhibiting NF-kappaB and MAPKs pathway activation in mice. International Immunopharmacology 75: 105749.
van der Velpen, V., A. Geelen, P.C. Hollman, E.G. Schouten, P. van’t Veer, and L.A. Afman. 2014. Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women. The American Journal of Clinical Nutrition 100: 1269–1277.
Choi, I., Y. Kim, Y. Park, H. Seog, and H. Choi. 2007. Anti-obesity activities of fermented soygerm isoflavones by Bifidobacterium breve. Biofactors 29: 105–112.
Seo, G.Y., Y. Lim, D. Koh, J.S. Huh, C. Hyun, Y.M. Kim, et al. 2017. TMF and glycitin act synergistically on keratinocytes and fibroblasts to promote wound healing and anti-scarring activity. Experimental & Molecular Medicine 49: e302.
Kim, E.Y., K.B. Hong, H.J. Suh, and H.S. Choi. 2015. Protective effects of germinated and fermented soybean extract against tert-butyl hydroperoxide-induced hepatotoxicity in HepG2 cells and in rats. Food & Function 6: 3512–3521.
Kang, K.A., R. Zhang, M.J. Piao, K.H. Lee, B.J. Kim, S.Y. Kim, H.S. Kim, D.H. Kim, H.J. You, and J.W. Hyun. 2007. Inhibitory effects of glycitein on hydrogen peroxide induced cell damage by scavenging reactive oxygen species and inhibiting c-Jun N-terminal kinase. Free Radical Research 41: 720–729.
Valachovicova, T., V. Slivova, H. Bergman, J. Shuherk, and D. Sliva. 2004. Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways. International Journal of Oncology 25: 1389–1395.
Zhang, B., H. Chen, J. Ouyang, Y. Xie, L. Chen, Q. Tan, et al. 2019. SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1beta and contributes to LIPUS-mediated anti-inflammatory effect. Autophagy: 1–17.
Li, W., W. Wang, L. Liu, R. Qu, X. Chen, C. Qiu, J. Li, J. Hayball, L. Liu, J. Chen, X. Wang, X. Pan, and Y. Zhao. 2019. GDF11 antagonizes TNF-alpha-induced inflammation and protects against the development of inflammatory arthritis in mice. The FASEB Journal 33: 3317–3329.
Hosseinzadeh, A., S.K. Kamrava, M.T. Joghataei, R. Darabi, A. Shakeri-Zadeh, M. Shahriari, R.J. Reiter, H. Ghaznavi, and S. Mehrzadi. 2016. Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin. Journal of Pineal Research 61: 411–425.
Dieppe, P., S. Goldingay, and M. Greville-Harris. 2016. The power and value of placebo and nocebo in painful osteoarthritis. Osteoarthritis and Cartilage 24: 1850–1857.
Nees, T.A., N. Rosshirt, T. Reiner, M. Schiltenwolf, and B. Moradi. 2019. Inflammation and osteoarthritis-related pain. Schmerz 33: 4–12.
Rainsford, K.D., A.L. Parke, M. Clifford-Rashotte, and W.F. Kean. 2015. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology 23: 231–269.
Mobasheri, A., Y. Henrotin, H.K. Biesalski, and M. Shakibaei. 2012. Scientific evidence and rationale for the development of curcumin and resveratrol as nutraceutricals for joint health. International Journal of Molecular Sciences 13: 4202–4232.
Rigoglou, S., and A.G. Papavassiliou. 2013. The NF-kappaB signalling pathway in osteoarthritis. The International Journal of Biochemistry & Cell Biology 45: 2580–2584.
Liang, H., H. Wang, L. Luo, S. Fan, L. Zhou, Z. Liu, S. Yao, X. Zhang, K. Zhong, H. Zhao, and Z. Zha. 2019. Toll-like receptor 4 promotes high glucose-induced catabolic and inflammatory responses in chondrocytes in an NF-kappaB-dependent manner. Life Sciences 228: 258–265.
Xie, L., H. Xie, C. Chen, Z. Tao, C. Zhang, and L. Cai. 2019. Inhibiting the PI3K/AKT/NF-kappaB signal pathway with nobiletin for attenuating the development of osteoarthritis: in vitro and in vivo studies. Food & Function 10: 2161–2175.
Li, X.H., J.C. Zhang, S.F. Sui, and M.S. Yang. 2005. Effect of daidzin, genistin, and glycitin on osteogenic and adipogenic differentiation of bone marrow stromal cells and adipocytic transdifferentiation of osteoblasts. Acta Pharmacologica Sinica 26: 1081–1086.
Li, H., D. Wang, Y. Yuan, and J. Min. 2017. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Research & Therapy 19: 248.
Guo, L., X. Wei, Z. Zhang, X. Wang, C. Wang, P. Li, et al. 2019. Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway. Arthritis Research & Therapy 21: 109.
Honvo, G., V. Leclercq, A. Geerinck, T. Thomas, N. Veronese, A. Charles, V. Rabenda, C. Beaudart, C. Cooper, J.Y. Reginster, and O. Bruyère. 2019. Safety of topical non-steroidal anti-inflammatory drugs in osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs & Aging 36: 45–64.
Funding
This work was supported by the Natural Science Foundation of Shandong Province (Grant Nos. ZR2019MH05, ZR2019MH075, and BS2015SW028), the Key Research and Development Projects of Shandong Province (Nos. 2015GSF118115 and 2019GSF108152), the Cross-disciplinary Fund of Shandong University (Grant No. 2018JC007), and the National Natural Science Foundation of China (Grant Nos. 81501880 and 81602761).
Author information
Authors and Affiliations
Contributions
Conceived and designed the experiments: Hao Li, Xin Pan.
Performed the experiments: Wenhan Wang, Ruitong Yang, Minfa Zhang, Jiayi Li, Jiangfan Peng, Mingyang Xu, Yunpeng Zhao.
Corresponding authors
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Wang, W., Yang, R., Zhang, M. et al. Glycitin Suppresses Cartilage Destruction of Osteoarthritis in Mice. Inflammation 43, 1312–1322 (2020). https://doi.org/10.1007/s10753-020-01210-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-020-01210-3