Browse > Article
http://dx.doi.org/10.14348/molcells.2017.2314

Adipose-Derived Stem Cells Suppress Inflammation Induced by IL-1β through Down-Regulation of P2X7R Mediated by miR-373 in Chondrocytes of Osteoarthritis  

Jin, Rilong (Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University)
Shen, Miaoda (Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University)
Yu, Liedao (Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University)
Wang, Xuanwei (Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University)
Lin, Xiangjin (Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University)
Abstract
Adipose-derived stem cells (ADSCs) were previously considered to have an anti-inflammatory effect, and Interleukin-$1{\beta}$ ($IL-1{\beta}$) was found to be a pro-inflammatory factor in chondrocytes, but the mechanism underlying ADSCs and $IL-1{\beta}$ is unclear. In this study, we investigate whether P2X7 receptor (P2X7R) signalling, regulated by microRNA 373 (miR-373), was involved in the ADSCs and $IL-1{\beta}$ mediated inflammation in osteoarthritis (OA). Chondrocytes were collected from 20 OA patients and 20 control participants, and ADSCs were collected from patients who had undergone abdominal surgery. The typical surface molecules of ASDCs were detected by flow cytometry. The level of nitric oxide (NO) was determined by Griess reagent. Concentrations of prostaglandin E2 (PGE2), interleukin 6 (IL-6), matrix metallopeptidase 3 (MMP-3) were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of IL-6, MMP-3, miR-373 and P2X7R were determined by real-time polymerase chain reaction (PCR), and Western blot was used to detect the protein expression of P2X7R. The typical potential characters of ADSCs were verified. In chondrocytes or OA tissues, the miR-373 expression level was decreased, but the P2X7R expression was increased. $IL-1{\beta}$ stimulation increased the level of inflammatory factors in OA chondrocytes, and ADSCs co-cultured with $IL-1{\beta}$-stimulated chondrocytes decreased the inflammation. OA chondrocytes transfected with the miR-373 inhibitor increased the inflammation level. The miR-373 mimic suppressed the inflammation by targeting P2X7R and regulated its expression, while its effect was reversed by overexpression of P2X7R. $IL-1{\beta}$ induced inflammation in OA chondrocytes, while ADSCs seemed to inhibit the expression of P2X7R that was regulated by miR-373 and involved in the anti-inflammatory process in OA.
Keywords
adipose-derived stem cells; chondrocytes; miR-373; osteoarthritis; P2X7R;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Takahashi, K., Goomer, R.S., Harwood, F., Kubo, T., Hirasawa, Y., and Amiel, D. (1999). The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. Osteoarthritis Cartilage 7, 182-190.   DOI
2 Van Lent, P.L., and Van den Berg, W.B. (2013). Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation? Arthritis. Res. Ther. 15, 112.   DOI
3 Yu, X., Su, B., Ge, P., Wang, Z., Li, S., Huang, B., Gong, Y., and Lin, J. (2015). Human adipose derived stem cells induced cell apoptosis and s phase arrest in bladder tumor. Stem Cells Int. 2015, 619290.
4 Yudoh, K., Nguyen, v.T., Nakamura, H., Hongo-Masuko, K., Kato, T., and Nishioka, K. (2005). Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function. Arthritis Res. Ther. 7, R380-391.   DOI
5 Tsezou, A. (2014). Osteoarthritis year in review (2014: genetics and genomics. Osteoarthritis Cartilage 22, 2017-2024.   DOI
6 Aguero, J., Hadri, L., Hammoudi, N., Leonardson, L., Hajjar, R.J., and Ishikawa, K. (2017). Inhaled gene transfer for pulmonary circulation. Methods Mol. Biol. 1521, 339-349.
7 Berenbaum, F. (2013). Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 21, 16-21.   DOI
8 Cruz, C.M., Rinna, A., Forman, H.J., Ventura, A.L., Persechini, P.M., and Ojcius, D.M. (2007). ATP activates a reactive oxygen speciesdependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J. Biol. Chem. 282, 2871-9.   DOI
9 Dave, M. and Amin, A.R. (2013). Yin-Yang regulation of prostaglandins and nitric oxide by PGD2 in human arthritis: reversal by celecoxib. Immunol. Lett. 152, 47-54.   DOI
10 Dinarello, C.A. (2009). Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 27, 519-550.   DOI
11 Jiang, L.B., Lee, S., Wang, Y., Xu, Q.T., Meng, D.H., and Zhang, J. (2016). Adipose-derived stem cells induce autophagic activation and inhibit catabolic response to pro-inflammatory cytokines in rat chondrocytes. Osteoarthritis Cartilage 24, 1071-1081.   DOI
12 Eichelser, C., Stuckrath, I., Muller, V., Milde-Langosch, K., Wikman, H., Pantel, K., and Schwarzenbach, H. (2014). Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients. Oncotarget 5, 9650-9563.   DOI
13 Fechner, H., Vetter, R., Kurreck, J., and Poller, W. (2017). Silencing genes in the heart. Methods Mol. Biol. 1521, 17-39.
14 Fu, Y., Lei, J., Zhuang, Y., Zhang, K., and Lu, D. (2016). Overexpression of HMGB1 A-box reduced IL-1beta-induced MMP expression and the production of inflammatory mediators in human chondrocytes. Exp. Cell Res. 349, 184-190.   DOI
15 Lai, J.H., Kajiyama, G., Smith, R.L., Maloney, W., and Yang, F. (2013). Stem cells catalyze cartilage formation by neonatal articular chondrocytes in 3D biomimetic hydrogels. Sci. Rep. 3, 3553.   DOI
16 Johnson, V.L., and Hunter, D.J. (2014). The epidemiology of osteoarthritis. Best Pract. Res. Clin. Rheumatol. 28, 5-15.   DOI
17 Karlsen, T.A., de Sourza, G.A., Odegaard, B., Engebretsen, L., and Brinchmann, J.E. (2016). microRNA-140 inhibits inflammation and stimulates chondrogenesis in a model of interleukin 1beta-induced osteoarthritis. Mol. Ther. Nucleic. Acids 5, e373.   DOI
18 Kim, E.H., and Heo, C.Y. (2014). Current applications of adiposederived stem cells and their future perspectives. World J. Stem Cells 6, 65-68.   DOI
19 Le Feuvre, R.A., Brough, D., Iwakura, Y., Takeda, K., and Rothwell, N. J. (2002). Priming of macrophages with lipopolysaccharide potentiates P2X7-mediated cell death via a caspase-1-dependent mechanism, independently of cytokine production. J. Biol. Chem. 277, 3210-3218.   DOI
20 Lambert, C., Dubuc, J.E., Montell, E., Verges, J., Munaut, C., Noel, A., and Henrotin, Y. (2014). Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane. Arthritis Rheumatol. 66, 960-968.   DOI
21 Lee, K.H., Goan, Y.G., Hsiao, M., Lee, C.H., Jian, S.H., Lin, J.T., Chen, Y.L., and Lu, P.J. (2009). MicroRNA-373 (miR-373) posttranscriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer. Exp. Cell Res. 315, 2529-2538.   DOI
22 Lohse, R., Krebs, W., Kunz, B., Mau, S., Raatzsch, H., Rothkope, M., and Vogler, H. (1975). [The complex documentation of bladder neoplasms by means of electronic data processing]. Z. Urol. Nephrol. 68, 241-250.
23 Song, J., Kim, D., Chun, C.H., and Jin, E.J. (2015). miR-370 and miR- 373 regulate the pathogenesis of osteoarthritis by modulating onecarbon metabolism via SHMT-2 and MECP-2, respectively. Aging Cell 14, 826-837.   DOI
24 MakkiI, M.S., and Haqqi, T.M. (2016). Histone deacetylase inhibitor vorinostat (SAHA) suppresses IL-1beta-induced matrix metallopeptidase-13 expression by inhibiting IL-6 in osteoarthritis chondrocyte. Am. J. Pathol. 186, 2701-2708.   DOI
25 Meng, X., Muller, V., Milde-langosch, K., Trillsch, F., Pantel, K., and Schwarzenbach, H. (2016). Circulating cell-free miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer. Adv. Exp. Med. Biol. 924, 3-8.
26 Papanagnou, P., Stivarou, T., and Tsironi, M. (2016). The role of miRNAs in common inflammatory arthropathies: osteoarthritis and gouty arthritis. Biomolecules 6, pii: E44.   DOI
27 Place, R.F., Li, L.C., Pookot, D., Noonan, E.J., and Dahiya, R. (2008). MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc. Natl. Acad. Sci. USA 105, 1608-1613.   DOI
28 Shi, L.B., Cai, H.X., Chen, L.K., Wu, Y., Zhu, S.A., Gong, X.N., Xia, Y.X., Ouyang, H.W., and Zou, X.H. (2014). Tissue engineered bulking agent with adipose-derived stem cells and silk fibroin microspheres for the treatment of intrinsic urethral sphincter deficiency. Biomaterials 35, 1519-1530.   DOI
29 Stone, A.V., Loeser, R.F., Vanderman, K.S., Long, D.L., Clark, S.C., and Ferguson, C.M. (2014). Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis. Osteoarthritis Cartilage 22, 264-274.   DOI