Effect of pterostilbene on oxidative stress induced apoptosis in chondrocytes

doi:10.3969/j.issn.2095-4344.2854

Abstract

Abstract:

BACKGROUND: A variety of antioxidants exhibit anti-arthritis effects by inhibiting the production of inflammatory factors. Pterostilbene is a powerful natural antioxidant; however, there is no report on its effect against oxidative stress in chondrocytes.

OBJECTIVE: To investigate the effect of pterostilbene on oxidative stress induced apoptosis in human chondrocytes．

METHODS: Normal human articular chondrocytes were cultured in medium containing different concentrations of pterostilbene (7.8- 32 000 μg/L) for 24 continuous hours to determine the optimal concentration of pterostilbene. Normal human articular chondrocytes cultured in vitro were randomized into control group, pterostilbene group (treatment with 125 μg/L pterostilbene), hydrogen peroxide (H₂O₂) group (treatment with 0.2 mmol/L H₂O₂), and H₂O₂ plus pterostilbene group (pretreatment with 125 μg/L pterostilbene followed by continuous treatment in the medium containing 125 μg/L pterostilbene and 0.2 mmol/L H₂O₂). After treating for 24 hours, the cell proliferation rate was detected by MTT experiment, the cell morphology and number by hematoxylin-eosin staining, the cell activity was measured by FDA/PI staining, and the changes of proteoglycan content were observed by saffron O staining. The expression of chondrogenesis marker genes aggrecan and type II collagenase 1 was detected by RT-PCR. An approval for the study protocol was validated by the Ethic Committee of the First Affiliated Hospital of Guangxi Medical University with an approval No. 201805008.

RESULTS AND CONCLUSION: The results of MTT assay showed that pterostilbene could significantly promote chondrocyte growth at 15.6-250 μg/L, especially at 125 μg/L. The results of hematoxylin-eosin staining and FDA/PI staining further showed that pterostilbene could inhibit H₂O₂-induced chondrocyte apoptosis, promote chondrocyte proliferation, and increase cell viability. The results of saffron O staining showed that pterostilbene promoted the secretion of proteoglycan by chondrocytes and inhibited the adverse effects of H₂O₂ on chondrocytes. The results of RT-PCR further revealed that pterostilbene could promote the expression of aggrecan and type II collagenase 1 genes in chondrocytes damaged by oxidative stress and improve the chondrocyte differentiation function. In conclusion, pterostilbene can promote chondrocyte proliferation and inhibit human articular chondrocyte apoptosis caused by oxidative stress.

Key words: cartilage, articular cartilage, pterostilbene, chondrocytes, apoptosis, oxidative stress, experiment

CLC Number:

Lin Yicai, Wu Zhengyuan, Luo Yingli, Yao Jun. Effect of pterostilbene on oxidative stress induced apoptosis in chondrocytes[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(32): 5092-5096.

Figures/Tables 5

References

[1] SCHAAP LA, PEETERS GM, DENNISON EM, et al. European Project on OSteoArthritis (EPOSA): methodological challenges in harmonization of existing data from five European population-based cohorts on aging.BMC Musculoskelet Disord. 2011;12:272.

[2] MARTÍNEZ-PÉREZ B, DE LA TORRE-DÍEZ I, LÓPEZ-CORONADO M. Mobile health applications for the most prevalent conditions by the World Health Organization: review and analysis.J Med Internet Res. 2013;15(6):e120.

[3] AL FAQEH H, NOR HAMDAN BM, CHEN HC, et al. The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model.Exp Gerontol. 2012;47(6):458-464.

[4] FENG K, CHEN Z, PENGCHENG L, et al. Quercetin attenuates oxidative stress-induced apoptosis via SIRT1/AMPK-mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model.J Cell Physiol. 2019;234(10):18192-18205.

[5] CHARLIER E, RELIC B, DEROYER C, et al. Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis.Int J Mol Sci. 2016;17(12). pii: E2146.

[6] LEPETSOS P, PAPAVASSILIOU AG.ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta. 2016;1862(4):576-591.

[7] ZHAI Y, BEHERA J, TYAGI SC. Hydrogen sulfide attenuates homocysteine-induced osteoblast dysfunction by inhibiting mitochondrial toxicity.J Cell Physiol. 2019;234(10):18602-18614.

[8] YE W, ZHU S, LIAO C, et al. Advanced oxidation protein products induce apoptosis of human chondrocyte through reactive oxygen species-mediated mitochondrial dysfunction and endoplasmic reticulum stress pathways.Fundam Clin Pharmacol. 2017;31(1):64-74.

[9] LI B, JIANG T, LIU H, et al. Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1-Nrf2-Are signaling pathway.J Cell Physiol. 2018;234(1):561-571.

[10] BURGOS RA, HANCKE JL, BERTOGLIO JC, et al. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol. 2009;28(8):931-946.

[11] LAZZARONI M. Gastrointestinal side-effects of traditional non-steroidal anti-inflammatory drugs and new formulations.Aliment Pharmacol Ther. 2004;20 Suppl 2:48-58.

[12] SCHNITZER TJ, BURMESTER GR, MYSLER E, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet.2004; 364(9435):665-674.

[13] SELLAM J. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.Nat Rev Rheumatol. 2010;6(11):625-635.

[14] ZENG L, WANG W, RONG XF, et al. Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model.Int Immunopharmacol. 2014;18(1):175-181.

[15] 姚顺晗,廖亮,覃家港,等.罗汉果皂苷V刺激成骨细胞增殖与分化[J].中国组织工程研究,2019,23(29):4701-4706.

[16] MCCORMACK D, MCFADDEN D. Pterostilbene and cancer: current review.J Surg Res. 2012;173(2):e53-61.

[17] RUIZ MJ, FERNÁNDEZ M, PICÓ Y, et al. Dietary administration of high doses of pterostilbene and quercetin to mice is not toxic.J Agric Food Chem. 2009;57(8):3180-3186.

[18] MCCORMACK D, MCFADDEN D. A review of pterostilbene antioxidant activity and disease modification.Oxid Med Cell Longev. 2013;2013:575482.

[19] MAGILL P, BYRNE DP, BAKER JF. Review article: Osteochondral reconstruction and grafting.J Orthop Surg (Hong Kong). 2011;19(1):93-98.

[20] STEADMAN JR, BRIGGS KK, RODRIGO JJ, et al. Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up.Arthroscopy. 2003;19(5):477-484.

[21] HASHIMOTO S, OCHS RL, KOMIYA S. Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis.Arthritis Rheum. 1998;41(9):1632-1638.

[22] ASADA S, FUKUDA K, NISHISAKA F, et al. Hydrogen peroxide induces apoptosis of chondrocytes; involvement of calcium ion and extracellular signal-regulated protein kinase.Inflamm Res. 2001;50(1):19-23.

[23] MATSUSHITA T, FUKUDA K, YAMAZAKI K, et al. Hypoxia-induced nitric oxide protects chondrocytes from damage by hydrogen peroxide. Inflamm Res. 2004;53(8):344-350.

[24] SHIM JH, KIM KH, CHO YS, et al. Protective effect of oxidative stress in HaCaT keratinocytes expressing E7 oncogene. Amino Acids. 2008; 34(1):135-141.

[25] MOON D, MCCORMACK D, MCDONALD D. Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro.J Surg Res. 2013;180(2):208-215.

[26] ZHANG L, ZHOU G, SONG W, et al. Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo.Apoptosis. 2012;17(1):25-36.

[27] CHIOU YS, TSAI ML, NAGABHUSHANAM K, et al. Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathwayJ Agric Food Chem. 2011;59(6):2725-2733.

[28] XUE EX, LIN JP, ZHANG Y, et al. Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway. Oncotarget.2017;8(26):41988-42000.