Glucosamine promotes chondrocyte proliferation via the Wnt/β‑catenin signaling pathway

Ma,Yuhuan; Zheng,Wenwei; Chen,Houhuang; Shao,Xiang; Lin,Pingdong; Liu,Xianxiang; Li,Xihai; Ye,Hongzhi

doi:10.3892/ijmm.2018.3587

Glucosamine promotes chondrocyte proliferation via the Wnt/β‑catenin signaling pathway

Authors:
- Yuhuan Ma
- Wenwei Zheng
- Houhuang Chen
- Xiang Shao
- Pingdong Lin
- Xianxiang Liu
- Xihai Li
- Hongzhi Ye
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Affiliations: College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
Published online on: March 22, 2018 https://doi.org/10.3892/ijmm.2018.3587
Pages: 61-70
Copyright: © Ma 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 the mechanism underlying the effects of glucosamine (GlcN) on the proliferation of chondrocytes isolated from the knee cartilage of Sprague‑Dawley rats. Chondrocytes were treated with various concentrations of GlcN or without GlcN. The effects of GlcN on chondrocyte proliferation were determined using reverse transcription‑polymerase chain reaction, western blot analysis and immunohistochemistry. The results indicated that GlcN significantly improved chondrocyte viability, accelerated G1/S transition during progression of the cell cycle and promoted the expression of cell cycle regulatory proteins, including cyclin D1, cyclin‑dependent kinase (CDK)4 and CDK6, thus indicating that GlcN may promote chondrocyte proliferation. Furthermore, GlcN upregulated the expression levels of Wnt‑4, Frizzled‑2 and β‑catenin, and downregulated the expression of glycogen synthase kinase‑3. GlcN also promoted β‑catenin translocation; β‑catenin is able to activate numerous downstream target genes, including cyclin D1. To determine the role of the Wnt/β‑catenin signaling pathway in chondrocyte proliferation, the Wnt/β‑catenin signaling pathway was inhibited using Dickkopf‑1 (DKK‑1), after which chondrocytes were treated with GlcN. The results demonstrated that the expression levels of β‑catenin and cyclin D1 were decreased in chondrocytes treated with DKK‑1 and GlcN. These results suggested that GlcN may promote chondrocyte proliferation via the Wnt/β‑catenin signaling pathway.

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1	Hada S, Kaneko H, Sadatsuki R, Liu L, Futami I, Kinoshita M, Yusup A, Saita Y, Takazawa Y, Ikeda H, et al: The degeneration and destruction of femoral articular cartilage shows a greater degree of deterioration than that of the tibial and patellar articular cartilage in early stage knee osteoarthritis: A cross-sectional study. Osteoarthritis Cartilage. 22:1583–1589. 2014. View Article : Google Scholar : PubMed/NCBI
2	Moo EK, Han SK, Federico S, Sibole SC, Jinha A, Abu Osman NA, Pingguan-Murphy B and Herzog W: Extracellular matrix integrity affects the mechanical behaviour of in-situ chondrocytes under compression. J Biomech. 47:1004–1013. 2014. View Article : Google Scholar : PubMed/NCBI
3	Gao Y, Liu S, Huang J, Guo W, Chen J, Zhang L, Zhao B, Peng J, Wang A, Wang Y, et al: The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. BioMed Res Int. 2014:6484592014. View Article : Google Scholar : PubMed/NCBI
4	Onumah OE, Jules GE, Zhao Y, Zhou L, Yang H and Guo Z: Overexpression of catalase delays G0/G1- to S-phase transition during cell cycle progression in mouse aortic endothelial cells. Free Radic Biol Med. 46:1658–1667. 2009. View Article : Google Scholar : PubMed/NCBI
5	Lamb R, Lehn S, Rogerson L, Clarke RB and Landberg G: Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity. Cell Cycle. 12:2384–2394. 2013. View Article : Google Scholar : PubMed/NCBI
6	Li X, Chen J, Liang W, Li H, Liu F, Weng X, Lin P, Chen W, Zheng C, Xu H, et al: Bushen Zhuangjin Decoction promotes chondrocyte proliferation by stimulating cell cycle progression. Exp Ther Med. 9:839–844. 2015. View Article : Google Scholar : PubMed/NCBI
7	Lin AC, Seeto BL, Bartoszko JM, Khoury MA, Whetstone H, Ho L, Hsu C, Ali SA and Alman BA: Modulating hedgehog signaling can attenuate the severity of osteoarthritis. Nat Med. 15:1421–1425. 2009. View Article : Google Scholar : PubMed/NCBI
8	Appleton CT, Usmani SE, Mort JS and Beier F: Rho/ROCK and MEK/ERK activation by transforming growth factor-alpha induces articular cartilage degradation. Lab Invest. 90:20–30. 2010. View Article : Google Scholar
9	Yuasa T, Otani T, Koike T, Iwamoto M and Enomoto-Iwamoto M: Wnt/beta-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes: Its possible role in joint degeneration. Lab Invest. 88:264–274. 2008. View Article : Google Scholar : PubMed/NCBI
10	Yasuhara R, Ohta Y, Yuasa T, Kondo N, Hoang T, Addya S, Fortina P, Pacifici M, Iwamoto M and Enomoto-Iwamoto M: Roles of β-catenin signaling in phenotypic expression and proliferation of articular cartilage superficial zone cells. Lab Invest. 91:1739–1752. 2011. View Article : Google Scholar : PubMed/NCBI
11	Rosenbluh J, Wang X and Hahn WC: Genomic insights into WNT/β-catenin signaling. Trends Pharmacol Sci. 35:103–109. 2014. View Article : Google Scholar
12	Wang Y, Li YP, Paulson C, Shao JZ, Zhang X, Wu M and Chen W: Wnt and the Wnt signaling pathway in bone development and disease. Front Biosci (Landmark Ed). 19:379–407. 2014. View Article : Google Scholar
13	Long F, Schipani E, Asahara H, Kronenberg H and Montminy M: The CREB family of activators is required for endochondral bone development. Development. 128:541–550. 2001.PubMed/NCBI
14	Miclea RL, Karperien M, Bosch CA, van der Horst G, van der Valk MA, Kobayashi T, Kronenberg HM, Rawadi G, Akçakaya P, Löwik CW, et al: Adenomatous polyposis coli-mediated control of beta-catenin is essential for both chondrogenic and osteogenic differentiation of skeletal precursors. BMC Dev Biol. 9:262009. View Article : Google Scholar : PubMed/NCBI
15	Nagaoka I, Igarashi M and Sakamoto K: Biological activities of glucosamine and its related substances. Adv Food Nutr Res. 65:337–352. 2012. View Article : Google Scholar : PubMed/NCBI
16	Reginster JY, Neuprez A, Lecart MP, Sarlet N and Bruyere O: Role of glucosamine in the treatment for osteoarthritis. Rheumatol Int. 32:2959–2967. 2012. View Article : Google Scholar : PubMed/NCBI
17	Salazar J, Bello L, Chávez M, Añez R, Rojas J and Bermúdez V: Glucosamine for osteoarthritis: Biological effects, clinical efficacy, and safety on glucose metabolism. Arthritis (Egypt). 2014:4324632014.
18	Henrotin Y and Lambert C: Chondroitin and glucosamine in the management of osteoarthritis: An update. Curr Rheumatol Rep. 15:3612013. View Article : Google Scholar : PubMed/NCBI
19	Li H, Li X, Liu G, Chen J, Weng X, Liu F, Xu H, Liu X and Ye H: Bauhinia championi (Benth.) Benth. polysaccharides upregulate Wnt/β-catenin signaling in chondrocytes. Int J Mol Med. 32:1329–1336. 2013. View Article : Google Scholar : PubMed/NCBI
20	Lin P, Weng X, Liu F, Ma Y, Chen H, Shao X, Zheng W, Liu X, Ye H and Li X: Bushen Zhuangjin decoction inhibits TM-induced chondrocyte apoptosis mediated by endoplasmic reticulum stress. Int J Mol Med. 36:1519–1528. 2015. View Article : Google Scholar : PubMed/NCBI
21	Weng X, Lin P, Liu F, Chen J, Li H, Huang L, Zhen C, Xu H, Liu X, Ye H, et al: Achyranthes bidentata polysaccharides activate the Wnt/β-catenin signaling pathway to promote chondrocyte proliferation. Int J Mol Med. 34:1045–1050. 2014. View Article : Google Scholar : PubMed/NCBI
22	Yu F, Li X, Cai L, Li H, Chen J, Wong X, Xu H, Zheng C, Liu X and Ye H: Achyranthes bidentata polysaccharides induce chondrocyte proliferation via the promotion of the G1/S cell cycle transition. Mol Med Rep. 7:935–940. 2013. View Article : Google Scholar : PubMed/NCBI
23	Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R and Ben-Ze'ev A: The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA. 96:5522–5527. 1999. View Article : Google Scholar : PubMed/NCBI
24	Huelsken J and Birchmeier W: New aspects of Wnt signaling pathways in higher vertebrates. Curr Opin Genet Dev. 11:547–553. 2001. View Article : Google Scholar : PubMed/NCBI
25	Chan BY, Fuller ES, Russell AK, Smith SM, Smith MM, Jackson MT, Cake MA, Read RA, Bateman JF, Sambrook PN, et al: Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis. Osteoarthritis Cartilage. 19:874–885. 2011. View Article : Google Scholar : PubMed/NCBI
26	Kim HT, Lo MY and Pillarisetty R: Chondrocyte apoptosis following intraarticular fracture in humans. Osteoarthritis Cartilage. 10:747–749. 2002. View Article : Google Scholar : PubMed/NCBI
27	D'Lima DD, Hashimoto S, Chen PC, Colwell CW Jr and Lotz MK: Human chondrocyte apoptosis in response to mechanical injury. Osteoarthritis Cartilage. 9:712–719. 2001. View Article : Google Scholar
28	Löwenheim H, Reichl J, Winter H, Hahn H, Simon C, Gültig K, Müller A, Zenner HP, Zimmermann U and Knipper M: In vitro expansion of human nasoseptal chondrocytes reveals distinct expression profiles of G1 cell cycle inhibitors for replicative, quiescent, and senescent culture stages. Tissue Eng. 11:64–75. 2005. View Article : Google Scholar : PubMed/NCBI
29	Sherr CJ: D-type cyclins. Trends Biochem Sci. 20:187–190. 1995. View Article : Google Scholar : PubMed/NCBI
30	Ghiani C and Gallo V: Inhibition of cyclin E-cyclin-dependent kinase 2 complex formation and activity is associated with cell cycle arrest and withdrawal in oligodendrocyte progenitor cells. J Neurosci. 21:1274–1282. 2001. View Article : Google Scholar : PubMed/NCBI
31	Jeon JH, Suh HN, Kim MO and Han HJ: Glucosamine-induced reduction of integrin β4 and plectin complex stimulates migration and proliferation in mouse embryonic stem cells. Stem Cells Dev. 22:2975–2989. 2013. View Article : Google Scholar : PubMed/NCBI
32	Yano F, Kugimiya F, Ohba S, Ikeda T, Chikuda H, Ogasawara T, Ogata N, Takato T, Nakamura K, Kawaguchi H, et al: The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Biochem Biophys Res Commun. 333:1300–1308. 2005. View Article : Google Scholar : PubMed/NCBI
33	Kikuchi A: Regulation of beta-catenin signaling in the Wnt pathway. Biochem Biophys Res Commun. 268:243–248. 2000. View Article : Google Scholar : PubMed/NCBI
34	Valenta T, Hausmann G and Basler K: The many faces and functions of β-catenin. EMBO J. 31:2714–2736. 2012. View Article : Google Scholar : PubMed/NCBI
35	Ye S, Wang J, Yang S, Xu W, Xie M, Han K, Zhang B and Wu Z: Specific inhibitory protein Dkk-1 blocking Wnt/β-catenin signaling pathway improve protectives effect on the extracellular matrix. J Huazhong Univ Sci Technolog Med Sci. 31:657–662. 2011. View Article : Google Scholar : PubMed/NCBI
36	Gifre L, Ruiz-Gaspà S, Monegal A, Nomdedeu B, Filella X, Guañabens N and Peris P: Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 57:272–276. 2013. View Article : Google Scholar : PubMed/NCBI