Calcitonin protects rat chondrocytes from IL‑1β injury via the Wnt/β‑catenin pathway

Bai,Mingxiao; Ge,Lei; Chen,Hui; Jin,Qunhua

doi:10.3892/etm.2019.7806

Calcitonin protects rat chondrocytes from IL‑1β injury via the Wnt/β‑catenin pathway

Authors:
- Mingxiao Bai
- Lei Ge
- Hui Chen
- Qunhua Jin
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Affiliations: School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Emergency Department, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Pediatrics, Rizhao City Traditional Chinese Medicine Hospital, Rizhao, Shandong 276800, P.R. China, Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: July 24, 2019 https://doi.org/10.3892/etm.2019.7806
Pages: 2079-2085
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated whether the Wnt/β‑catenin pathway was involved in the protective effect of calcitonin (CT) in interleukin‑1β (IL‑1β)‑injured rat chondrocytes. Chondrocytes were acquired from the articular cartilage of 4‑week‑old rats and treated with 10 ng/ml IL‑1β to stimulate an in vitro osteoarthritis model. CT (10 and 50 nM) and 5 µm IWR‑1‑endo (a Wnt/β‑catenin inhibitor) was used for treatment. The proliferation and apoptosis of rat articular chondrocytes were measured using a cell counting kit‑8 assay and Annexin V/PI staining, respectively. Expression of matrix‑metalloproteinases (MMP)‑13 MMP3 and MMP9 and aggrecanases [metalloproteinase thrombospondin motifs (ADAMTS4 and ADAMTS5)] were measured to assess the degradation of the cartilage extracellular matrix. The results of the present study demonstrate that CT protected rat chondrocytes from IL‑1β stimulation by enhancing cell viability, suppressing apoptosis and decreasing the expression of matrix metallopeptidase (MMP) MMP13, MMP3, MMP9, ADAMTS4 and ADAMTS5. CT treatment also upregulated dickkopf‑1 and downregulated β‑catenin. IWR‑1‑endo demonstrated similar effects to that of CT treatment. The administration of CT in addition to IWR‑1‑endo reinforced the change trends induced by CT or IWR‑1‑endo in the aforementioned events, indicating that CT possibly acted via the Wnt/β‑catenin pathway to exert a protective effect on IL‑1β‑injured rat chondrocytes.

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1	Yimam M, Lee YC, Wright L, Jiao P, Horm T, Hong M, Brownell L and Jia Q: A botanical composition mitigates cartilage degradations and pain sensitivity in osteoarthritis disease model. J Med Food. 20:568–576. 2017. View Article : Google Scholar : PubMed/NCBI
2	Ickinger C and Tikly M: Current approach to diagnosis and management of osteoarthritis. SA Fam Pract. 52:382–390. 2010.
3	Karsdal MA, Sondergaard BC, Arnold M and Christiansen C: Calcitonin affects both bone and cartilage: A dual action treatment for osteoarthritis? Ann N Y Acad Sci. 1117:181–195. 2007. View Article : Google Scholar : PubMed/NCBI
4	Zhang LB, Man ZT, Li W, Zhang W, Wang XQ and Sun S: Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-κB pathways. Mol Immunol. 87:249–257. 2017. View Article : Google Scholar : PubMed/NCBI
5	Yan XL, Wei LJ, Wang WY and Zhang L: Effect of calcitonin on the inflammatory reaction in IL-1β-induced chondrocytes in rats. Jie Fang Jun Yi Xue Za Zhi. 24:47–51. 2015.(In Chinese).
6	Zhou Y, Wang T, Hamilton JL and Chen D: Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis. Curr Rheumatol Rep. 19:532017. View Article : Google Scholar : PubMed/NCBI
7	Rossini M, Gatti D and Adami S: Involvement of WNT/β-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int. 93:121–132. 2013. View Article : Google Scholar : PubMed/NCBI
8	Liu HY and Zheng Y: A study on Wnt/β-catenin signal pathway in rabbit models with osteoarthritis. Feng Shi Bing Yu Guan Jie Yan. 4:5–8. 2015.(In Chinese).
9	Zhang YN, Wang WY, Zhang L, Hu HY, Li B and Wang ZY: Effect of calcitonin on beta-catenin and secreted frizzled-related protein 1 in articular cartilages. Zhong Guo Zu Zhi Gong Cheng Yan Jiu Lin Chuang Kang Fu. 14:7601–7604. 2010.(In Chinese).
10	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
11	Alcaraz MJ, Megías J, García-Arnandis I, Clérigues V and Guillén MI: New molecular targets for the treatment of osteoarthritis. Biochem Pharmacol. 80:13–21. 2010. View Article : Google Scholar : PubMed/NCBI
12	Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP and Fahmi H: Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 7:33–42. 2011. View Article : Google Scholar : PubMed/NCBI
13	Jacques C, Recklies AD, Levy A and Berenbaum F: HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II collagen expressions. Osteoarthritis Cartilage. 15:138–146. 2007. View Article : Google Scholar : PubMed/NCBI
14	Zou J, Li XL, Shi ZM and Xue JF: Effects of C-myc gene silencing on interleukin-1β-induced rat chondrocyte cell proliferation, apoptosis and cytokine expression. J Bone Miner Metab. 36:286–296. 2018. View Article : Google Scholar : PubMed/NCBI
15	You X: The experimental research of the effects of calcitonin on cytokines and apoptosis of articular chondrocytes during the development of knee osteoarthritis in rabbits. Chin J Osteoporosis. 18:223–228. 2012.(In Chinese).
16	Greco KV, Nalesso G, Kaneva MK, Sherwood J, Iqbal AJ, Moradi-Bidhendi N, Dell'Accio F and Perretti M: Analyses on the mechanisms that underlie the chondroprotective properties of calcitonin. Biochem Pharmacol. 91:348–358. 2014. View Article : Google Scholar : PubMed/NCBI
17	Sumer EU, Qvist P and Tankó LB: Matrix metalloproteinase and aggrecanase generated aggrecan fragments: Implications for the diagnostics and therapeutics of destructive joint diseases. Drug Dev Res. 68:1–13. 2007. View Article : Google Scholar
18	Cheng T, Zhang L, Fu X, Wang W, Xu H, Song H and Zhang Y: The potential protective effects of calcitonin involved in coordinating chondrocyte response, extracellular matrix, and subchondral trabecular bone in experimental osteoarthritis. Connect Tissue Res. 54:139–146. 2013. View Article : Google Scholar : PubMed/NCBI
19	Li J, Xie ZG, Xie Y and Dong QR: Calcitonin treatment is associated with less severe osteoarthritis and reduced toll-like receptor levels in a rat model. J Orthop Sci. 19:1019–1027. 2014. View Article : Google Scholar : PubMed/NCBI
20	Enochson L, Stenberg J, Brittberg M and Lindahl A: GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition. Osteoarthritis Cartilage. 22:566–577. 2014. View Article : Google Scholar : PubMed/NCBI
21	Zhang YN: Effect of calcitonin on articular cartilage chondrocytes of osteoarthritis. Journal. 2009.