Astragaloside IV protects against apoptosis in human degenerative chondrocytes through autophagy activation

Liu,Jianhong; Meng,Qinggang; Jing,Hanguang; Zhou,Sheng

doi:10.3892/mmr.2017.6980

Astragaloside IV protects against apoptosis in human degenerative chondrocytes through autophagy activation

Authors:
- Jianhong Liu
- Qinggang Meng
- Hanguang Jing
- Sheng Zhou
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Affiliations: System Complexity Research Center of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
Published online on: July 14, 2017 https://doi.org/10.3892/mmr.2017.6980
Pages: 3269-3275
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increased cell apoptosis in chondrocytes is a feature of degenerative cartilage. Astragaloside IV (AST) has been proven to possess an antiarthritic effect by preventing interleukin (IL)‑1β‑induced cartilage damage. However, the role of AST on chondrocyte apoptosis and its underlying mechanism remains unknown. In the present study, degenerative chondrocytes isolated from patients with osteoarthritis (OA) were subjected to AST and IL‑1β treatment. Results indicated that AST protected against chondrocyte apoptosis induced by IL‑1β. Western blotting indicated that AST increased the protein expression of LC3‑II/I and decreased P62/SQSTM1 expression, which suggested that AST upregulated autophagy activity in chondrocytes. Fluorescent protein GFP‑LC3 analysis and transmission electron microscopy observation confirmed that autophagy was promoted by AST. In contrast, after autophagy inhibited by 3‑methyladenine, chondrocyte apoptosis was further increased under IL‑1β treatment. Ultimately, rapamycin was used as a positive control, whose results confirmed that rapamycin‑mediated autophagy also decreased chondrocyte apoptosis induced by IL‑1β. In conclusion, these results suggested that AST‑mediated autophagy serves an anti‑apoptotic role in chondrocytes, which may aid the development of novel therapeutic approaches for OA treatment.

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1	Xie F, Kovic B, Jin X, He X, Wang M and Silvestre C: Economic and humanistic burden of osteoarthritis: A systematic review of large sample studies. Pharmacoeconomics. 34:1087–1100. 2016. View Article : Google Scholar : PubMed/NCBI
2	Zamli Z and Sharif M: Chondrocyte apoptosis: A cause or consequence of osteoarthritis? Int J Rheum Dis. 14:159–166. 2011. View Article : Google Scholar : PubMed/NCBI
3	Wojdasiewicz P, Poniatowski ŁA and Szukiewicz D: The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014:5614592014. View Article : Google Scholar : PubMed/NCBI
4	He Y, Du M, Gao Y, Liu H, Wang H, Wu X and Wang Z: Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels. PLoS One. 8:e764952013. View Article : Google Scholar : PubMed/NCBI
5	Wang B and Chen MZ: Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage. Arch Pharm Res. 37:793–802. 2014. View Article : Google Scholar : PubMed/NCBI
6	Rockel JS and Kapoor M: Autophagy: Controlling cell fate in rheumatic diseases. Nat Rev Rheumatol. 12:517–531. 2016. View Article : Google Scholar : PubMed/NCBI
7	Li YS, Zhang FJ, Zeng C, Luo W, Xiao WF, Gao SG and Lei GH: Autophagy in osteoarthritis. Joint Bone Spine. 83:143–148. 2016. View Article : Google Scholar : PubMed/NCBI
8	Almonte-Becerril M, Navarro-Garcia F, Gonzalez-Robles A, Vega-Lopez MA, Lavalle C and Kouri JB: Cell death of chondrocytes is a combination between apoptosis and autophagy during the pathogenesis of Osteoarthritis within an experimental model. Apoptosis. 15:631–638. 2010. View Article : Google Scholar : PubMed/NCBI
9	Sasaki H, Takayama K, Matsushita T, Ishida K, Kubo S, Matsumoto T, Fujita N, Oka S, Kurosaka M and Kuroda R: Autophagy modulates osteoarthritis-related gene expression in human chondrocytes. Arthritis Rheum. 64:1920–1928. 2012. View Article : Google Scholar : PubMed/NCBI
10	Lu Y, Li S, Wu H, Bian Z, Xu J, Gu C, Chen X and Yang D: Beneficial effects of astragaloside IV against angiotensin II-induced mitochondrial dysfunction in rat vascular smooth muscle cells. Int J Mol Med. 36:1223–1232. 2015.PubMed/NCBI
11	Xu J and Zhang C: In vitro isolation and cultivation of human chondrocytes for osteoarthritis renovation. In Vitro Cell Dev Biol Anim. 50:623–629. 2014. View Article : Google Scholar : PubMed/NCBI
12	Philp AM, Davis ET and Jones SW: Developing anti-inflammatory therapeutics for patients with osteoarthritis. Rheumatology (Oxford). 56:869–881. 2017.PubMed/NCBI
13	Liu R, Jiang H, Tian Y, Zhao W and Wu X: Astragaloside IV protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes. J Surg Res. 200:315–323. 2016. View Article : Google Scholar : PubMed/NCBI
14	Cho WC and Leung KN: In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus. J Ethnopharmacol. 113:132–141. 2007. View Article : Google Scholar : PubMed/NCBI
15	Zhang Y, Vasheghani F, Li YH, Blati M, Simeone K, Fahmi H, Lussier B, Roughley P, Lagares D, Pelletier JP, et al: Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis. Ann Rheum Dis. 74:1432–1440. 2015. View Article : Google Scholar : PubMed/NCBI
16	Caramés B, Olmer M, Kiosses WB and Lotz MK: The relationship of autophagy defects to cartilage damage during joint aging in a mouse model. Arthritis Rheumatol. 67:1568–1576. 2015. View Article : Google Scholar : PubMed/NCBI
17	Chiu BY, Chang CP, Lin JW, Yu JS, Liu WP, Hsu YC and Lin MT: Beneficial effect of astragalosides on stroke condition using PC12 cells under oxygen glucose deprivation and reperfusion. Cell Mol Neurobiol. 34:825–837. 2014. View Article : Google Scholar : PubMed/NCBI
18	Levine B and Yuan J: Autophagy in cell death: An innocent convict? J Clin Invest. 115:2679–2688. 2005. View Article : Google Scholar : PubMed/NCBI
19	Huang ZM, Du SH, Huang LG, Li JH, Xiao L and Tong P: Leptin promotes apoptosis and inhibits autophagy of chondrocytes through upregulating lysyl oxidase-like 3 during osteoarthritis pathogenesis. Osteoarthritis Cartilage. 24:1246–1253. 2016. View Article : Google Scholar : PubMed/NCBI
20	Ma B, Leijten JC, Wu L, Kip M, van Blitterswijk CA, Post JN and Karperien M: Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture. Osteoarthritis Cartilage. 21:599–603. 2013. View Article : Google Scholar : PubMed/NCBI