Protocatechuic acid alleviates degeneration of chondrocytes

doi:10.3969/j.issn.2095-4344.2486

Abstract

Abstract:

BACKGROUND: Preliminary studies have shown that numerous antioxidants exhibit antiarthritic effects due to their inhibition on inflammatory factors. With the antioxidant and anti-inflammatory abilities whether protocatechuic acid is effective in the treatment of osteoarthritis has never been reported.

OBJECTIVE: To investigate the biological effect of protocatechuic acid on interleukin-1β induced chondrocyte including phenotype and cellular metabolism in vitro, thereby providing a potential agent in osteoarthritis treatment.

METHODS: The chondrocytes of neonatal rat femur were collected, intervened by 10 mg/L interleukin-1β to establish the degenerative model, and treated by 10, 30 and 50 mg/L protocatechuic acid. The study was approved by the Laboratory Animal Ethical Committee of Guangxi Medical University in October 2017, with the approval No. 201710008.

RESULTS AND CONCLUSION: Protocatechuic acid effectively promoted chondrocyte growth in the range of 10-50 mg/L, while the dose of 30 mg/L was the strongest. Protocatechuic acid also enhanced the synthesis of the extracellular matrix and the mRNA expression of aggrecan, collagen II and Sox9, and downregulating the expression of the matrix metalloproteinase 13 (a marker of inflammatory factor). To conclude, protocatechuic acid exerts a positive effect on the proliferation and phenotypic maintenance of articular chondrocytes, providing reference for its use in the treatment of osteoarthritis and repair of degenerative articular cartilage in vivo.

Key words: protocatechuic acid, chondrocyte, osteoarthritis, collagen type II, proliferation, antiinflammatory, cartilage protective agent, chondrocyte phenotype

CLC Number:

Zhan Long, Meng Nongqin, Nong Juan, Li Xiaofeng, Yang Yuan, Yu Xue.

Protocatechuic acid alleviates degeneration of chondrocytes [J]. Chinese Journal of Tissue Engineering Research, 2020, 24(8): 1149-1154.

Figures/Tables 8

References

[1] GOLDRING MB. Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract Res Clin Rheumatol. 2006;20(5):1003-1025.
[2] MOLLON B, KANDEL R, CHAHAL J, et al. The clinical status of cartilage tissue regeneration in humans. Osteoarthritis Cartilage. 2013;21(12):1824-1833.
[3] GARGIULO S, GAMBA P, POLI G, et al. Metalloproteinases and metalloproteinase inhibitors in age-related diseases. Curr Pharm Des. 2014;20(18):2993-3018.
[4] NELSON FRT. The value of phenotypes in knee osteoarthritis research. Open Orthop J. 2018;12:105-114.
[5] ZHOU PH, QIU B, DENG RH, et al. Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model. Cell Physiol Biochem. 2018; 47(3):1207-1216.
[6] MASELLA R, SANTANGELO C, D'ARCHIVIO M, et al. Protocatechuic acid and human disease prevention: biological activities and molecular mechanisms. Curr Med Chem. 2012;19(18):2901-2917.
[7] LIN HH, CHEN JH, CHOU FP, et al. Protocatechuic acid inhibits cancer cell metastasis involving the down-regulation of Ras/Akt/NF-κB pathway and MMP-2 production by targeting RhoB activation. Br J Pharmacol. 2011;162(1): 237-254.
[8] 陈颖娟,黄慈波,牛素平,等.骨关节炎患者关节软骨细胞合成和分解基因的表达研究[J].风湿病与关节炎,2016,5(5):5-8,31.
[9] 刘庆珍,吴尽,邳晓盟,等.软骨发育过程中负调控Sox9基因表达机制研究进展[J].农业科学与技术(英文版),2017,18(6): 1038-1041.
[10] 陈克明,葛宝丰,刘兴炎,等.骨软骨组织中Ⅰ､Ⅱ型胶原基因表达的检测[J].西北国防医学杂志,2000,21(3):216-218.
[11] PFANDER D, SWOBODA B, KIRSCH T. Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes. Am J Pathol. 2001; 159(5):1777-1783.
[12] WU J, TAO Y, SHANG A, et al. Effect of the interaction between MiR-200b-3p and DNMT3A on cartilage cells of osteoarthritis patients. J Cell Mol Med. 2017;21(10): 2308-2316.
[13] TSUCHIYA H, KITOH H, SUGIURA F, et al. Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells. Biochem Biophys Res Commun. 2003;301(2):338-343.
[14] MA B, LEIJTEN JC, WU L, et al. Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture. Osteoarthritis Cartilage. 2013;21(4):599-603.
[15] 张加雄,屈巧玲,王凌.高效液相色谱法同时测定四季青中4种酚酸类成分的含量[J].西南国防医药,2010,20(6):611-613.
[16] WANG HY, WANG H, WANG JH, et al. Protocatechuic Acid Inhibits Inflammatory Responses in LPS-Stimulated BV2 Microglia via NF-κB and MAPKs Signaling Pathways. Neurochem Res. 2015;40(8):1655-1660.
[17] GUAN S, GE D, LIU TQ, et al. Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in cultured neural stem cells. Toxicol In Vitro. 2009;23(2):201-208.
[18] FOSANG AJ, BEIER F. Emerging Frontiers in cartilage and chondrocyte biology. Best Pract Res Clin Rheumatol. 2011; 25(6):751-766.
[19] GAN L, KANDEL RA. In vitro cartilage tissue formation by Co-culture of primary and passaged chondrocytes. Tissue Eng. 2007;13(4):831-842.
[20] CHOI WS, YANG JI, KIM W, et al. Critical role for arginase II in osteoarthritis pathogenesis. Ann Rheum Dis. 2019;78(3): 421-428.
[21] HU ZC, GONG LF, LI XB, et al. Inhibition of PI3K/Akt/NF-κB signaling with leonurine for ameliorating the progression of osteoarthritis: In vitro and in vivo studies. J Cell Physiol. 2019; 234(5):6940-6950.
[22] MURAHASHI Y, YANO F, KOBAYASHI H, et al. Intra-articular administration of IκBα kinase inhibitor suppresses mouse knee osteoarthritis via downregulation of the NF-κB/HIF-2α axis. Sci Rep. 2018;8(1):16475.