Paeoniflorin inhibits IL‑1β‑induced MMP secretion via the NF‑κB pathway in chondrocytes

Hu,Peng‑Fei; Sun,Fang‑Fang; Jiang,Li‑Feng; Bao,Jia‑Peng; Wu,Li‑Dong

doi:10.3892/etm.2018.6325

Paeoniflorin inhibits IL‑1β‑induced MMP secretion via the NF‑κB pathway in chondrocytes

Authors:
- Peng‑Fei Hu
- Fang‑Fang Sun
- Li‑Feng Jiang
- Jia‑Peng Bao
- Li‑Dong Wu
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Affiliations: Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Cancer Institute, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
Published online on: June 19, 2018 https://doi.org/10.3892/etm.2018.6325
Pages: 1513-1519

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Abstract

Paeoniflorin serves important cellular roles, exerting anti‑cancer, anti‑inflammatory and anti‑pulmonary fibrosis effects and possesses immune‑modulatory properties. However, the exact role of paeoniflorin in the pathogenesis of osteoarthritis (OA) remains unclear. The aim of the present study was to investigate the effects of paeoniflorin on articular surfaces in vitro. Rat chondrocytes were cultured in vitro and an MTT assay was performed to assess chondrocyte survival. Following treatment with interleukin (IL)‑1β and paeoniflorin, the production of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases‑1 (TIMP‑1) was examined using reverse transcription‑quantitative polymerase chain reaction and western blotting. The interleukin (IL)‑1β‑induced nuclear factor (NF)‑κB pathway activation was also investigated. The results demonstrated that paeoniflorin was able to downregulate the expression of MMP and increase the expression of TIMP‑1ntmRNA and protein in IL‑1β‑induced rat chondrocytes. Furthermore, treating chondrocytes with paeoniflorin blocked the activation of NF‑κB. These results suggest that paeoniflorin may serve am anti‑catabolic role in the progression of OA and may be an effective preventative treatment for OA.

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1	Hunter DJ and Felson DT: Osteoarthritis. BMJ. 332:639–642. 2006. View Article : Google Scholar : PubMed/NCBI
2	Kamimura M, Nakamura Y, Uchiyama S, Ikegami S, Mukaiyama K and Kato H: The pathophysiology and progression of hip osteoarthritis accompanied with joint pain are potentially due to bone alterations-follow-up study of hip oa patients. Open Rheumatol J. 8:46–53. 2014. View Article : Google Scholar : PubMed/NCBI
3	Smith GN Jr: The role of collagenolytic matrix metalloproteinases in the loss of articular cartilage in osteoarthritis. Fron Biosci. 11:3081–3095. 2006. View Article : Google Scholar
4	Burrage PS, Mix KS and Brinckerhoff CE: Matrix metalloproteinases: Role in arthritis. Front Biosci. 11:529–543. 2006. View Article : Google Scholar : PubMed/NCBI
5	Naito K, Takahashi M, Kushida K, Suzuki M, Ohishi T, Miura M, Inoue T and Nagano A: Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: Comparison with generalized osteoarthritis. Rheumatology (Oxford). 38:510–515. 1999. View Article : Google Scholar : PubMed/NCBI
6	Aida Y, Maeno M, Suzuki N, Shiratsuchi H, Motohashi M and Matsumura H: The effect of IL-1beta on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes. Life Sci. 77:3210–3221. 2005. View Article : Google Scholar : PubMed/NCBI
7	Kobayashi M, Squires GR, Mousa A, Tanzer M, Zukor DJ, Antoniou J, Feige U and Poole AR: Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum. 52:128–135. 2005. View Article : Google Scholar : PubMed/NCBI
8	Shibata S, Aimi N and Watanabe M: Paeoniflorin, a monoterpene glucoside of chinese paeony root. Tetrahedron Lett. 5:1991–1995. 1964. View Article : Google Scholar
9	Gu X, Cai Z, Cai M, Liu K, Liu D, Zhang Q, Tan J and Ma Q: Protective effect of paeoniflorin on inflammation and apoptosis in the cerebral cortex of a transgenic mouse model of Alzheimer's disease. Mol Med Rep. 13:2247–2252. 2016. View Article : Google Scholar : PubMed/NCBI
10	Ji Y, Dou YN, Zhao QW, Zhang JZ, Yang Y, Wang T, Xia YF, Dai Y and Wei ZF: Paeoniflorin suppresses TGF-β mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway. Acta Pharmacol Sin. 37:794–804. 2016. View Article : Google Scholar : PubMed/NCBI
11	Hao J, Yang X, Ding XL, Guo LM, Zhu CH, Ji W, Zhou T and Wu XZ: Paeoniflorin potentiates the inhibitory effects of erlotinib in pancreatic cancer cell lines by reducing ErbB3 phosphorylation. Sci Rep. 6:328092016. View Article : Google Scholar : PubMed/NCBI
12	Shi L, Teng H, Zhu M, Li C, Huang K, Chen BI, Dai Y and Wang J: Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration. Exp Ther Med. 10:257–262. 2015. View Article : Google Scholar : PubMed/NCBI
13	Chang Y, Jia X, Wei F, Wang C, Sun X, Xu S, Yang X, Zhao Y, Chen J, Wu H, et al: CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage. Sci Rep. 6:262392016. View Article : Google Scholar : PubMed/NCBI
14	Thirion S and Berenbaum F: Culture and phenotyping of chondrocytes in primary culture. Methods Mol Med. 100:1–14. 2004.PubMed/NCBI
15	Hu PF, Chen WP, Tang JL, Bao JP and Wu LD: Protective effects of berberine in an experimental rat osteoarthritis model. Phytother Res. 25:878–885. 2011. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Hu PF, Chen WP, Tang JL, Bao JP and Wu LD: Apelin plays a catabolic role on articular cartilage: In vivo and in vitro studies. Int J Mol Med. 26:357–363. 2010.PubMed/NCBI
18	Liu H, Wang J, Wang J, Wang P and Xue Y: Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways. Brain Res. 1618:149–158. 2015. View Article : Google Scholar : PubMed/NCBI
19	Wang S and Liu W: Paeoniflorin inhibits proliferation and promotes apoptosis of multiple myeloma cells via its effects on microRNA29b and matrix metalloproteinase2. Mol Med Rep. 14:2143–2149. 2016. View Article : Google Scholar : PubMed/NCBI
20	Liu Q, Lin X, Li H, Yuan J, Peng Y, Dong L and Dai S: Paeoniflorin ameliorates renal function in cyclophosphamide-induced mice via AMPK suppressed inflammation and apoptosis. Biomed Pharmacother. 84:1899–1905. 2016. View Article : Google Scholar : PubMed/NCBI
21	Chen C, Du P and Wang J: Paeoniflorin ameliorates acute myocardial infarction of rats by inhibiting inflammation and inducible nitric oxide synthase signaling pathways. Mol Med Rep. 12:3937–3943. 2015. View Article : Google Scholar : PubMed/NCBI
22	He DY and Dai SM: Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall., a traditional chinese herbal medicine. Front Pharmacol. 2:102011. View Article : Google Scholar : PubMed/NCBI
23	Li PP, Liu DD, Liu YJ, Song SS, Wang QT, Chang Y, Wu YJ, Chen JY, Zhao WD, Zhang LL and Wei W: BAFF/BAFF-R involved in antibodies production of rats with collagen-induced arthritis via PI3K-Akt-mTOR signaling and the regulation of paeoniflorin. J Ethnopharmacol. 141:290–300. 2012. View Article : Google Scholar : PubMed/NCBI
24	Jia Z and He J: Paeoniflorin ameliorates rheumatoid arthritis in rat models through oxidative stress, inflammation and cyclooxygenase 2. Exp Ther Med. 11:655–659. 2016. View Article : Google Scholar : PubMed/NCBI
25	Wu D, Chen J, Zhu H, Xiong XG, Liang QH, Zhang Y, Zhang Y, Wang Y, Yang B and Huang X: UPLC-PDA determination of paeoniflorin in rat plasma following the oral administration of radix paeoniae alba and its effects on rats with collagen-induced arthritis. Exp Ther Med. 7:209–217. 2014. View Article : Google Scholar : PubMed/NCBI
26	Yang N, Cui H, Han F, Zhang L, Huang T, Zhou Y and Zhou J: Paeoniflorin inhibits human pancreatic cancer cell apoptosis via suppression of MMP-9 and ERK signaling. Oncol Lett. 12:1471–1476. 2016. View Article : Google Scholar : PubMed/NCBI
27	Zhao L, Chang Q, Huang T and Huang C: Paeoniflorin inhibits IL1β-induced expression of inflammatory mediators in human osteoarthritic chondrocyte. Mol Med Rep. 17:3306–3311. 2018.PubMed/NCBI
28	Burrage PS and Brinckerhoff CE: Molecular targets in osteoarthritis: Metalloproteinases and their inhibitors. Curr Drug Targets. 8:293–303. 2007. View Article : Google Scholar : PubMed/NCBI
29	Jo H, Park JS, Kim EM, Jung MY, Lee SH, Seong SC, Park SC, Kim HJ and Lee MC: The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes. Osteoarthritis Cartilage. 11:585–594. 2003. View Article : Google Scholar : PubMed/NCBI
30	Tchetverikov I, Lohmander LS, Verzijl N, Huizinga TW, TeKoppele JM, Hanemaaijer R and DeGroot J: MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis. 64:694–698. 2005. View Article : Google Scholar : PubMed/NCBI
31	Goupille P, Jayson MI, Valat JP and Freemont AJ: Matrix metalloproteinases: The clue to intervertebral disc degeneration? Spine (Phila Pa 1976). 23:1612–1626. 1998. View Article : Google Scholar : PubMed/NCBI
32	Little CB, Barai A, Burkhardt D, Smith SM, Fosang AJ, Werb Z, Shah M and Thompson EW: Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum. 60:3723–3733. 2009. View Article : Google Scholar : PubMed/NCBI
33	Li NG, Shi ZH, Tang YP, Wang ZJ, Song SL, Qian LH, Qian DW and Duan JA: New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr Med Chem. 18:977–1001. 2011. View Article : Google Scholar : PubMed/NCBI
34	Daheshia M and Yao JQ: The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J Rheumatol. 35:2306–2312. 2008. View Article : Google Scholar : PubMed/NCBI
35	Martel-Pelletier J, Alaaeddine N and Pelletier JP: Cytokines and their role in the pathophysiology of osteoarthritis. Front Biosci. 4:D694–D703. 1999. View Article : Google Scholar : PubMed/NCBI
36	Wu DQ, Zhong HM, Ding QH and Ba L: Protective effects of biochanin A on articular cartilage: In vitro and in vivo studies. BMC Complement Altern Med. 14:4442014. View Article : Google Scholar : PubMed/NCBI
37	Roman-Blas JA and Jimenez SA: NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 14:839–848. 2006. View Article : Google Scholar : PubMed/NCBI
38	Rigoglou S and Papavassiliou AG: The NF-κB signalling pathway in osteoarthritis. Int J Biochem Cell Biol. 45:2580–2584. 2013. View Article : Google Scholar : PubMed/NCBI
39	Ono R, Kaisho T and Tanaka T: PDLIM1 inhibits NF-κB-mediated inflammatory signaling by sequestering the p65 subunit of NF-κB in the cytoplasm. Sci Rep. 5:183272015. View Article : Google Scholar : PubMed/NCBI
40	Wu H, Li W, Wang T, Shu Y and Liu P: Paeoniflorin suppress NF-kappaB activation through modulation of I kappaB alpha and enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomed Pharmacother. 62:659–666. 2008. View Article : Google Scholar : PubMed/NCBI
41	Huch K, Stove J, Puhl W and Gunther KP: Review and comparison of culture-techniques for articular chondrocytes. Z Orthop Ihre Grenzgeb. 140:145–152. 2002.(In German). View Article : Google Scholar : PubMed/NCBI