Effect of emodin on chondrocyte viability in an in vitro model of osteoarthritis

Liu,Zhenfeng; Lang,Yi; Li,Li; Liang,Zhiquan; Deng,Yingjie; Fang,Rui; Meng,Qingcai

doi:10.3892/etm.2018.6877

Effect of emodin on chondrocyte viability in an in vitro model of osteoarthritis

Authors:
- Zhenfeng Liu
- Yi Lang
- Li Li
- Zhiquan Liang
- Yingjie Deng
- Rui Fang
- Qingcai Meng
View Affiliations

Affiliations: Department of Orthopedics, Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830000, P.R. China
Published online on: October 18, 2018 https://doi.org/10.3892/etm.2018.6877
Pages: 5384-5389

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Emodin is an anthraquinone isolated from the Chinese herb Radix et Rhizoma Rhei and has been used to treat various diseases for centuries. The aim of the present study was to investigate the effect of emodin on the inflammatory mediators in rat chondrocytes. In the present study, chondrocytes were isolated from rats, cultured and harvested when they reached generation P3. Cells were treated with different doses of emodin (10, 20, and 30 µg/ml) followed by interleukin 1β (IL‑1β, 10 ng/ml). Control cells were either untreated or treated with IL‑1β alone. An enzyme‑linked immunosorbent assay was used to measure levels of nitric oxide (NO) and prostaglandin E2 (PGE2). Reverse transcription‑quantitative polymerase chain was performed to measure levels of matrix metallopeptidase (MMP)‑3 and ‑13 mRNA. The expression of MMP‑3, MMP‑13, extracellular‑signal regulatory kinase (ERK)1/2, phosphorylated ERK1/2 and β‑catenin proteins were detected by western‑blot analysis. The results demonstrated that treatment with emodin treatment reduced the cytotoxicity of IL‑1β and inhibited the expression of NO and PGE2 in rat chondrocytes. Furthermore, emodin inhibited the expression of MMP3 and MMP13, and the phosphorylation of various proteins involved in the ERK and Wnt/β‑catenin pathway. Therefore, emodin is able to promote the proliferation of chondrocytes by inhibiting the ERK and Wnt/β‑catenin pathway and downregulating the expression of a series of inflammatory mediators in chondrocytes.

View Figures

View References

1	Kang X, Fransen M, Zhang Y, Li H, Ke Y, Lu M, Su S, Song X, Guo Y, Chen J, et al: The high prevalence of knee osteoarthritis in a rural Chinese population: The Wuchuan osteoarthritis study. Arthritis Rheum. 61:641–647. 2009. View Article : Google Scholar : PubMed/NCBI
2	Zhang Y, Xu L, Nevitt MC, Aliabadi P, Yu W, Qin M, Lui LY and Felson DT: Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: The Beijing osteoarthritis study. Arthritis Rheum. 44:2065–2071. 2001. View Article : Google Scholar : PubMed/NCBI
3	Fernandes JC, Martel-Pelletier J and Pelletier JP: The role of cytokines in osteoarthritis pathophysiology. Biorheology. 39:237–246. 2002.PubMed/NCBI
4	Lotz M: Cytokines in cartilage injury and repair. Clin Orthop Relat Res. (391 Suppl):S108–S115. 2001. View Article : Google Scholar : PubMed/NCBI
5	Goldring MB and Otero M: Inflammation in osteoarthritis. Curr Opin Rheumatol. 23:471–478. 2011. View Article : Google Scholar : PubMed/NCBI
6	Wojdasiewicz P and Poniatowski ŁA and Szukiewicz D: The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014:ID 561459. 2014. View Article : Google Scholar : PubMed/NCBI
7	Qu Y, Zhou L and Wang C: Effects of platycodin D on IL-1β-induced inflammatory response in human osteoarthritis chondrocytes. Int Immunopharmacol. 40:474–479. 2016. View Article : Google Scholar : PubMed/NCBI
8	Mobasheri A: The future of osteoarthritis therapeutics: Targeted pharmacological therapy. Curr Rheumatol Rep. 15:3642013. View Article : Google Scholar : PubMed/NCBI
9	He K, Ye X, Wu H, Wang Y, Zou Z, Ning N, Hu Y, Chen B, Fang X and Li X: The safety and anti-hypercholesterolemic effect of emodin in Syrian golden hamsters. Lipids. 50:185–194. 2015. View Article : Google Scholar : PubMed/NCBI
10	Lin S, Chen H, Wei W, Ye S, Liao W, Gong J, Jiang Z, Wang L and Lin S: Antiproliferative and antimetastatic effects of emodin on human pancreatic cancer. Oncol Rep. 26:81–89. 2011.PubMed/NCBI
11	Gu JW, Hasuo H, Takeya M and Akasu T: Effects of emodin on synaptic transmission in rat hippocampal CA1 pyramidal neurons in vitro. Neuropharmacology. 49:103–111. 2005. View Article : Google Scholar : PubMed/NCBI
12	Meng G, Liu Y, Lou C and Yang H: Emodin suppresses lipopolysaccharide-induced pro-inflammatory responses and NF-κB activation by disrupting lipid rafts in CD14-negative endothelial cells. Br J Pharmacol. 161:1628–1644. 2010. View Article : Google Scholar : PubMed/NCBI
13	Zhou PH, Liu SQ and Peng H: The effect of hyaluronic acid on IL-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis. J Orthop Res. 26:1643–1648. 2008. View Article : Google Scholar : PubMed/NCBI
14	Chowdhury TT, Bader DL and Lee DA: Dynamic compression inhibits the synthesis of nitric oxide and PGE(2) by IL-1beta-stimulated chondrocytes cultured in agarose constructs. Biochem Biophys Res Commun. 285:1168–1174. 2001. View Article : Google Scholar : PubMed/NCBI
15	Poole AR, Ionescu M, Fitzcharles MA and Billinghurst RC: The assessment of cartilage degradation in vivo: Development of an immunoassay for the measurement in body fluids of type II collagen cleaved by collagenases. J Immunol Methods. 294:145–153. 2004. View Article : Google Scholar : PubMed/NCBI
16	Guha M and Mackman N: LPS induction of gene expression in human monocytes. Cell Signal. 13:85–94. 2001. View Article : Google Scholar : PubMed/NCBI
17	Corr M: Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. Nat Clin Pract Rheumatol. 4:550–556. 2008. View Article : Google Scholar : PubMed/NCBI
18	Vincenti MP: The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression. Methods Mol Biol. 151:121–148. 2001.
19	Nagase H and Woessner JF Jr: Matrix metalloproteinases. J Biol Chem. 274:21491–21494. 1999. View Article : Google Scholar : PubMed/NCBI
20	Zhu X, Zeng K, Qiu Y, Yan F and Lin C: Therapeutic effect of emodin on collagen-induced arthritis in mice. Inflammation. 36:1253–1259. 2013. View Article : Google Scholar : PubMed/NCBI
21	Galasso O, Familiari F, De Gori M and Gasparini G: Recent findings on the role of gelatinases (matrix metalloproteinase-2 and −9) in osteoarthritis. Adv Orthop 2012. Article ID 834208. 2012. View Article : Google Scholar
22	Wang M, Sampson ER, Jin H, Li J, Ke QH, Im HJ and Chen D: MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis Res Ther. 15:R52013. View Article : Google Scholar : PubMed/NCBI
23	Vincenti MP and Brinckerhoff CE: Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: Integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res. 4:157–164. 2002. View Article : Google Scholar : PubMed/NCBI
24	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
25	Ha MK, Song YH, Jeong SJ, Lee HJ, Jung JH, Kim B, Song HS, Huh JE and Kim SH: Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1 in hypoxic rheumatoid synoviocytes. Biol Pharm Bull. 34:1432–1437. 2011. View Article : Google Scholar : PubMed/NCBI
26	Hwang JK, Noh EM, Moon SJ, Kim JM, Kwon KB, Park BH, You YO, Hwang BM, Kim HJ, Kim BS, et al: Emodin suppresses inflammatory responses and joint destruction in collagen-induced arthritic mice. Rheumatology (Oxford). 52:1583–1591. 2013. View Article : Google Scholar : PubMed/NCBI
27	Krens SF, Spaink HP and Snaar-Jagalska BE: Functions of the MAPK family in vertebrate-development. FEBS Lett. 580:4984–4990. 2006. View Article : Google Scholar : PubMed/NCBI