Effect of resveratrol on high mobility group box-1 protein signaling pathway in cartilage endplate degeneration caused by inflammation_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

HU Hua ,  LI Liantai , LIU Yanwei , WANG Shujun , XIE Shuangxi , SUN Jianjun

Department of Orthopedics, Affiliated Hospital of Chengde Medical College, Chengde Hebei, 067000, P. R. China;

Corresponding author：

LI Liantai, Email: liliantai369@163.com

Keywords：

Resveratrol; cartilage endplate; degeneration; high mobility group box-1 protein; signaling pathway; rat

DOI：

10.7507/1002-1892.202110084

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of resveratrol (RES) on inflammation-induced cartilage endplate (CEP) degeneration, and its regulatory mechanism on high mobility group box-1 protein (HMGB1) signaling pathway. Methods The intervertebral CEP cells of Sprague Dawley (SD) rats aged 3 weeks were extracted and identified by toluidine blue staining and immunofluorescence staining of rabbit anti-rat collagen type Ⅱ. The cell counting kit 8 (CCK-8) method was used to screen the optimal concentration of RES on intervertebral CEP cells. Gene chip analysis was used to determine the target of RES on intervertebral CEP cells. Interleukin 1β (IL-1β) was used to construct the intervertebral CEP cell degeneration model caused by inflammation and the 7-8-week-old SD rat intervertebral disc degeneration model, and pcDNA3.1-HMGB1 (pcDNA3.1) was used as the control of RES effect. Flow cytometry and TUNEL staining were used to detect the apoptotic rate of intervertebral CEP cells and rat intervertebral disc tissue cells, respectively. ELISA kit was used to detect the content of interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) in the cell supernatant and rat serum. Western blot was used to detect the expressions of HMGB1, extracellular signal-regulated protein kinase (ERK), phosphorylated ERK (p-ERK), B cell lymphoma/leukemia 2 gene (Bcl-2), and Bcl-2-associated X protein (Bax). Results The extracted cells were identified as rat intervertebral CEP cells. CCK-8 method screened out the highest activity of intervertebral CEP cells treated with 30 μmol/L RES. The gene chip analysis confirmed that the HMGB1-ERK signal was the target of RES. Both cell experiments and animal experiments showed that RES treatment can significantly down-regulate the apoptosis rate of intervertebral CEP cells, inhibit the release of TNF-α, and increase the content of IL-10; and down-regulate the expressions of HMGB1, p-ERK, and Bax, and increase Bcl-2; and pcDNA3.1 could partially reverse these effects of RES, and the differences were all significant (P<0.05). Conclusion RES can significantly inhibit the apoptosis of intervertebral CEP cells induced by inflammation, which is related to inhibiting the expression of HMGB1.

Citation： HU Hua, LI Liantai, LIU Yanwei, WANG Shujun, XIE Shuangxi, SUN Jianjun. Effect of resveratrol on high mobility group box-1 protein signaling pathway in cartilage endplate degeneration caused by inflammation. Chinese Journal of Reparative and Reconstructive Surgery, 2022, 36(4): 461-469. doi: 10.7507/1002-1892.202110084 Copy

1.	Kirnaz S, Capadona C, Lintz M, et al. Pathomechanism and biomechanics of degenerative disc disease: Features of healthy and degenerated discs. Int J Spine Surg, 2021, 15(s1): 10-25.
2.	Yang RZ, Xu WN, Zheng HL, et al. Involvement of oxidative stress-induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis. J Cell Physiol, 2021, 236(4): 2725-2739.
3.	Wang Y, Shi Y, Huang Y, et al. Resveratrol mediates mechanical allodynia through modulating inflammatory response via the TREM2-autophagy axis in SNI rat model. J Neuroinflammation, 2020, 17(1): 311. doi: 10.1186/s12974-020-01991-2.
4.	Feng Y, Hu S, Liu L, et al. HMGB1 contributes to osteoarthritis of temporomandibular joint by inducing synovial angiogenesis. J Oral Rehabil, 2021, 48(5): 551-559.
5.	Shen P, Lin W, Ba X, et al. Quercetin-mediated SIRT1 activation attenuates collagen-induced mice arthritis. J Ethnopharmacol, 2021, 279: 114213. doi: 10.1016/j.jep.2021.114213.
6.	Fan W, Chen S, Wu X, et al. Resveratrol relieves gouty arthritis by promoting mitophagy to inhibit activation of NLRP3 inflammasomes. J Inflamm Res, 2021, 14: 3523-3536.
7.	Shao Z, Wang B, Shi Y, et al. Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis. Osteoarthritis Cartilage, 2021, 29(3): 413-422.
8.	李文超, 林一峰, 梁祖建, 等. 鹿茸多肽对软骨终板细胞基质蛋白及其降解酶基因表达的影响. 中国中医骨伤科杂志, 2019, 27(1): 6-10, 16.
9.	Freidin M, Kraatari M, Skarp S, et al. Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes. J Med Genet, 2019, 56(7): 420-426.
10.	Ding J, Zhang R, Li H, et al. ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration. Aging (Albany NY), 2021, 13(7): 10703-10723.
11.	Zhao Y, Qiu C, Wang W, et al. Cortistatin protects against intervertebral disc degeneration through targeting mitochondrial ROS-dependent NLRP3 inflammasome activation. Theranostics, 2020, 10(15): 7015-7033.
12.	Jiang Y, Luo W, Wang B, et al. Resveratrol promotes osteogenesis via activating SIRT1/FoxO1 pathway in osteoporosis mice. Life Sci, 2020, 246: 117422. doi: 10.3389/fcell.2020.00694.
13.	Kim H, Hong JY, Lee J, et al. IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model. Spine J, 2021, 21(6): 1031-1041.
14.	Jie J, Xu X, Li W, et al. Regulation of apoptosis and inflammatory response in interleukin-1β-induced nucleus pulposus cells by miR-125b-5p via targeting TRIAP1. Biochem Genet, 2021, 59(2): 475-490.
15.	Grujić-Milanović J, Jaćević V, Miloradović Z, et al. Resveratrol protects cardiac tissue in experimental malignant hypertension due to antioxidant, anti-inflammatory, and anti-apoptotic properties. Int J Mol Sci, 2021, 22(9): 5006. doi: 10.3390/ijms22095006.
16.	Wang B, Ji D, Xing W, et al. miR-142-3p and HMGB1 are negatively regulated in proliferation, apoptosis, migration, and autophagy of cartilage endplate cells. Cartilage, 2021, 13(2_suppl): 592S-603S.
17.	Hassanpour M, Biray Avci Ç, Rahbarghazi R, et al. Resveratrol reduced the detrimental effects of malondialdehyde on human endothelial cells. J Cardiovasc Thorac Res, 2021, 13(2): 131-140.
18.	Gorth DJ, Ottone OK, Shapiro IM, et al. Differential effect of long-term systemic exposure of TNFα on health of the annulus fibrosus and nucleus pulposus of the intervertebral disc. J Bone Miner Res, 2020, 35(4): 725-737.
19.	Ping SH, Tian FM, Liu H, et al. Raloxifene inhibits the overexpression of TGF-β₁ in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis. Bosn J Basic Med Sci, 2021, 21(3): 284-293.
20.	Tang N, Dong Y, Xiao T, et al. LncRNA TUG1 promotes the intervertebral disc degeneration and nucleus pulposus cell apoptosis though modulating miR-26a/HMGB1 axis and regulating NF-κB activation. Am J Transl Res, 2020, 12(9): 5449-5464.
21.	Su Q, Li Y, Feng X, et al. Association and histological characteristics of endplate injury and intervertebral disc degeneration in a rat model. Injury, 2021, 52(8): 2084-2094.
22.	Liu L, Zhang J, Zhang X, et al. HMGB1: an important regulator of myeloid differentiation and acute myeloid leukemia as well as a promising therapeutic target. J Mol Med (Berl), 2021, 99(1): 107-118.
23.	Liu N, Wu Y, Wen X, et al. Chronic stress promotes acute myeloid leukemia progression through HMGB1/NLRP3/IL-1β signaling pathway. J Mol Med (Berl), 2021, 99(3): 403-414.
24.	Sgrignani J, Cecchinato V, Fassi EMA, et al. Systematic development of peptide inhibitors targeting the CXCL12/HMGB1 interaction. J Med Chem, 2021, 64(18): 13439-13450.
25.	Huang J, Zeng T, Zhang X, et al. Clinical diagnostic significance of 14-3-3η protein, high-mobility group box-1, anti-cyclic citrullinated peptide antibodies, anti-mutated citrullinated vimentin antibodies and rheumatoid factor in rheumatoid arthritis. Br J Biomed Sci, 2020, 77(1): 19-23.
26.	贺亚军, 孙麟, 冯浩宇, 等. 甘草甜素抑制高迁移率族蛋白B1对大鼠脊髓损伤后胶质瘢痕形成的作用及机制研究. 中国修复重建外科杂志, 2020, 34(10): 1298-1304.
27.	Kawakubo A, Uchida K, Miyagi M, et al. Investigation of resident and recruited macrophages following disc injury in mice. J Orthop Res, 2020, 38(8): 1703-1709.

1. Kirnaz S, Capadona C, Lintz M, et al. Pathomechanism and biomechanics of degenerative disc disease: Features of healthy and degenerated discs. Int J Spine Surg, 2021, 15(s1): 10-25.
2. Yang RZ, Xu WN, Zheng HL, et al. Involvement of oxidative stress-induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis. J Cell Physiol, 2021, 236(4): 2725-2739.
3. Wang Y, Shi Y, Huang Y, et al. Resveratrol mediates mechanical allodynia through modulating inflammatory response via the TREM2-autophagy axis in SNI rat model. J Neuroinflammation, 2020, 17(1): 311. doi: 10.1186/s12974-020-01991-2.
4. Feng Y, Hu S, Liu L, et al. HMGB1 contributes to osteoarthritis of temporomandibular joint by inducing synovial angiogenesis. J Oral Rehabil, 2021, 48(5): 551-559.
5. Shen P, Lin W, Ba X, et al. Quercetin-mediated SIRT1 activation attenuates collagen-induced mice arthritis. J Ethnopharmacol, 2021, 279: 114213. doi: 10.1016/j.jep.2021.114213.
6. Fan W, Chen S, Wu X, et al. Resveratrol relieves gouty arthritis by promoting mitophagy to inhibit activation of NLRP3 inflammasomes. J Inflamm Res, 2021, 14: 3523-3536.
7. Shao Z, Wang B, Shi Y, et al. Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis. Osteoarthritis Cartilage, 2021, 29(3): 413-422.
8. 李文超, 林一峰, 梁祖建, 等. 鹿茸多肽对软骨终板细胞基质蛋白及其降解酶基因表达的影响. 中国中医骨伤科杂志, 2019, 27(1): 6-10, 16.
9. Freidin M, Kraatari M, Skarp S, et al. Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes. J Med Genet, 2019, 56(7): 420-426.
10. Ding J, Zhang R, Li H, et al. ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration. Aging (Albany NY), 2021, 13(7): 10703-10723.
11. Zhao Y, Qiu C, Wang W, et al. Cortistatin protects against intervertebral disc degeneration through targeting mitochondrial ROS-dependent NLRP3 inflammasome activation. Theranostics, 2020, 10(15): 7015-7033.
12. Jiang Y, Luo W, Wang B, et al. Resveratrol promotes osteogenesis via activating SIRT1/FoxO1 pathway in osteoporosis mice. Life Sci, 2020, 246: 117422. doi: 10.3389/fcell.2020.00694.
13. Kim H, Hong JY, Lee J, et al. IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model. Spine J, 2021, 21(6): 1031-1041.
14. Jie J, Xu X, Li W, et al. Regulation of apoptosis and inflammatory response in interleukin-1β-induced nucleus pulposus cells by miR-125b-5p via targeting TRIAP1. Biochem Genet, 2021, 59(2): 475-490.
15. Grujić-Milanović J, Jaćević V, Miloradović Z, et al. Resveratrol protects cardiac tissue in experimental malignant hypertension due to antioxidant, anti-inflammatory, and anti-apoptotic properties. Int J Mol Sci, 2021, 22(9): 5006. doi: 10.3390/ijms22095006.
16. Wang B, Ji D, Xing W, et al. miR-142-3p and HMGB1 are negatively regulated in proliferation, apoptosis, migration, and autophagy of cartilage endplate cells. Cartilage, 2021, 13(2_suppl): 592S-603S.
17. Hassanpour M, Biray Avci Ç, Rahbarghazi R, et al. Resveratrol reduced the detrimental effects of malondialdehyde on human endothelial cells. J Cardiovasc Thorac Res, 2021, 13(2): 131-140.
18. Gorth DJ, Ottone OK, Shapiro IM, et al. Differential effect of long-term systemic exposure of TNFα on health of the annulus fibrosus and nucleus pulposus of the intervertebral disc. J Bone Miner Res, 2020, 35(4): 725-737.
19. Ping SH, Tian FM, Liu H, et al. Raloxifene inhibits the overexpression of TGF-β₁ in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis. Bosn J Basic Med Sci, 2021, 21(3): 284-293.
20. Tang N, Dong Y, Xiao T, et al. LncRNA TUG1 promotes the intervertebral disc degeneration and nucleus pulposus cell apoptosis though modulating miR-26a/HMGB1 axis and regulating NF-κB activation. Am J Transl Res, 2020, 12(9): 5449-5464.
21. Su Q, Li Y, Feng X, et al. Association and histological characteristics of endplate injury and intervertebral disc degeneration in a rat model. Injury, 2021, 52(8): 2084-2094.
22. Liu L, Zhang J, Zhang X, et al. HMGB1: an important regulator of myeloid differentiation and acute myeloid leukemia as well as a promising therapeutic target. J Mol Med (Berl), 2021, 99(1): 107-118.
23. Liu N, Wu Y, Wen X, et al. Chronic stress promotes acute myeloid leukemia progression through HMGB1/NLRP3/IL-1β signaling pathway. J Mol Med (Berl), 2021, 99(3): 403-414.
24. Sgrignani J, Cecchinato V, Fassi EMA, et al. Systematic development of peptide inhibitors targeting the CXCL12/HMGB1 interaction. J Med Chem, 2021, 64(18): 13439-13450.
25. Huang J, Zeng T, Zhang X, et al. Clinical diagnostic significance of 14-3-3η protein, high-mobility group box-1, anti-cyclic citrullinated peptide antibodies, anti-mutated citrullinated vimentin antibodies and rheumatoid factor in rheumatoid arthritis. Br J Biomed Sci, 2020, 77(1): 19-23.
26. 贺亚军, 孙麟, 冯浩宇, 等. 甘草甜素抑制高迁移率族蛋白B1对大鼠脊髓损伤后胶质瘢痕形成的作用及机制研究. 中国修复重建外科杂志, 2020, 34(10): 1298-1304.
27. Kawakubo A, Uchida K, Miyagi M, et al. Investigation of resident and recruited macrophages following disc injury in mice. J Orthop Res, 2020, 38(8): 1703-1709.

Chinese Journal of Reparative and Reconstructive Surgery

Effect of resveratrol on high mobility group box-1 protein signaling pathway in cartilage endplate degeneration caused by inflammation

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content