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Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1

  • Authors:
    • Ying Kong
    • Wanchun Wang
    • Changjie Zhang
    • Yi Wu
    • Yang Liu
    • Xiaorong Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
    Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4569-4576
    |
    Published online on: April 15, 2016
       https://doi.org/10.3892/mmr.2016.5137
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Abstract

A central feature of osteoarthritis (OA) is the loss of articular cartilage, which is primarily attributed to cartilage breakdown. A group of metalloproteinases termed the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family are reported to be important in cartilage breakdown. Recent studies have suggested that ADAMTS‑4 is a major contributor to the pathogenesis of OA and that syndecan‑1 is closely associated with activation of ADAMTS‑4 in human chondrocytes. Accumulating evidence also suggests that cannabinoids have chondroprotective effects. The current study explored the effects of synthetic cannabinoid WIN‑55,212‑2 mesylate (WIN‑55) on the expression of syndecan‑1 and ADAMTS‑4, as well as ADAMTS‑4 activity, in unstimulated and interleukin (IL)‑1β‑stimulated OA chondrocytes. Primary human OA articular chondrocytes were treated with WIN‑55 in the presence or absence of IL‑1β and cannabinoid receptor antagonists. The results of the present study demonstrated that WIN‑55 inhibited ADAMTS‑4 activity in unstimulated and IL‑1β‑stimulated primary human OA articular chondrocytes in a concentration‑dependent manner. Cannabinoid receptor type 1 (CB1) and 2 (CB2) were constitutively expressed in human OA articular chondrocytes. Furthermore, selective CB2 antagonist, JTE907, but not selective CB1 antagonist, MJ15, abolished the inhibitory effect of WIN‑55 on ADAMTS‑4 activity. WIN55 inhibited the expression of syndecan‑1 but not ADAMTS‑4, and overexpression of syndecan‑1 reversed the inhibitory effect of WIN‑55 on the ADAMTS‑4 activity in unstimulated and IL‑1β‑stimulated human OA articular chondrocytes. Despite having no significant effect on syndecan‑1 gene promoter activity, WIN‑55 markedly decreased the stability of syndecan‑1 mRNA via CB2. In conclusion, to the best of our knowledge, the present study provides the first in vitro evidence supporting that the synthetic cannabinoid WIN‑55 inhibits ADAMTS‑4 activity in unstimulated and IL‑1β‑stimulated human OA articular chondrocytes by decreasing the mRNA stability/expression of syndecan‑1 via CB2. This suggests a novel mechanism by which cannabinoids may prevent cartilage breakdown in OA. In addition, it also provides novel insights into the pharmacological effects of synthetic cannabinoids on OA.
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View References

1 

Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, et al: National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum. 58:26–35. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Goldring MB and Goldring SR: Osteoarthritis. J Cell Physiol. 213:626–634. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Xue J, Wang J, Liu Q and Luo A: Tumor necrosis factor-α induces ADAMTS-4 expression in human osteoarthritis chondrocytes. Mol Med Rep. 8:1755–1760. 2013.PubMed/NCBI

4 

Matsukawa T, Sakai T, Yonezawa T, Hiraiwa H, Hamada T, Nakashima M, Ono Y, Ishizuka S, Nakahara H, Lotz MK, et al: MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes. Arthritis Res Ther. 15:R282013. View Article : Google Scholar : PubMed/NCBI

5 

Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G and Pap T: Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat Med. 15:1072–1076. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC and Griggs DW: Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum. 56:575–585. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Barre PE, Redini F, Boumediene K, Vielpeau C and Pujol JP: Semiquantitative reverse transcription-polymerase chain reaction analysis of syndecan-1 and -4 messages in cartilage and cultured chondrocytes from osteoarthritic joints. Osteoarthritis Cartilage. 8:34–43. 2000. View Article : Google Scholar

8 

Tkachenko E, Rhodes JM and Simons M: Syndecans: New kids on the signaling block. Circ Res. 96:488–500. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Molténi A, Modrowski D, Hott M and Marie PJ: Differential expression of fibroblast growth factor receptor-1, -2, and -3 and syndecan-1, -2, and -4 in neonatal rat mandibular condyle and calvaria during osteogenic differentiation in vitro. Bone. 24:337–347. 1999. View Article : Google Scholar : PubMed/NCBI

10 

Gao G, Plaas A, Thompson VP, Jin S, Zuo F and Sandy JD: ADAMTS4 (aggrecanase-1) activation on the cell surface involves C-terminal cleavage by glycosylphosphatidyl inositol-anchored membrane type 4-matrix metalloproteinase and binding of the activated proteinase tochondroitin sulfate and heparan sulfate on syndecan-1. J Biol Chem. 279:10042–10051. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Dunn SL, Wilkinson JM, Crawford A, Le Maitre CL and Bunning RA: Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1β induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes. Osteoarthritis Cartilage. 2:133–144. 2014. View Article : Google Scholar

12 

Mbvundula EC, Bunning RA and Rainsford KD: Arthritis and cannabinoids: HU-210 and Win-55,212-2 prevent IL-1alpha-induced matrix degradation in bovine articular chondrocytes in-vitro. J Pharm Pharmacol. 58:351–358. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Dunn SL, Wilkinson JM, Crawford A and Le Maitre CL: Novel therapies for arthritis? Future Med Chem. 4:713–725. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Moncada-Pazos A, Obaya AJ, Viloria CG, López-Otín C and Cal S: The nutraceutical flavonoid luteolin inhibits ADAMTS-4 and ADAMTS-5 aggrecanase activities. J Mol Med Berl. 89:611–619. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Tauchi R, Imagama S, Natori T, Ohgomori T, Muramoto A, Shinjo R, Matsuyama Y, Ishiguro N and Kadomatsu K: The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury. J Neuroinflammation. 9:532012. View Article : Google Scholar : PubMed/NCBI

16 

Doyle A and Griffiths JB: Cell and Tissue Culture: Laboratory Procedures. Cell Quantification. John Wiley & Sons, Inc; Chichester, England: pp. 58–59. 1998

17 

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

18 

Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, et al: International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: Beyond CB and CB1 and CB2. Pharmacol Rev. 62:588–631. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Sun Y, Alexander SP, Kendall DA and Bennett AJ: Cannabinoids and PPARalpha signalling. Biochem Soc Trans. 34:1095–1097. 2006. View Article : Google Scholar : PubMed/NCBI

20 

O'Sullivan SE and Kendall DA: Cannabinoid activation of peroxisome proliferator-activated receptors: Potential for modulation of inflammatory disease. Immunobiology. 215:611–616. 2010. View Article : Google Scholar

21 

Goldring MB and Marcu KB: Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther. 11:2242009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kong Y, Wang W, Zhang C, Wu Y, Liu Y and Zhou X: Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1. Mol Med Rep 13: 4569-4576, 2016.
APA
Kong, Y., Wang, W., Zhang, C., Wu, Y., Liu, Y., & Zhou, X. (2016). Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1. Molecular Medicine Reports, 13, 4569-4576. https://doi.org/10.3892/mmr.2016.5137
MLA
Kong, Y., Wang, W., Zhang, C., Wu, Y., Liu, Y., Zhou, X."Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1". Molecular Medicine Reports 13.6 (2016): 4569-4576.
Chicago
Kong, Y., Wang, W., Zhang, C., Wu, Y., Liu, Y., Zhou, X."Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1". Molecular Medicine Reports 13, no. 6 (2016): 4569-4576. https://doi.org/10.3892/mmr.2016.5137
Copy and paste a formatted citation
x
Spandidos Publications style
Kong Y, Wang W, Zhang C, Wu Y, Liu Y and Zhou X: Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1. Mol Med Rep 13: 4569-4576, 2016.
APA
Kong, Y., Wang, W., Zhang, C., Wu, Y., Liu, Y., & Zhou, X. (2016). Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1. Molecular Medicine Reports, 13, 4569-4576. https://doi.org/10.3892/mmr.2016.5137
MLA
Kong, Y., Wang, W., Zhang, C., Wu, Y., Liu, Y., Zhou, X."Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1". Molecular Medicine Reports 13.6 (2016): 4569-4576.
Chicago
Kong, Y., Wang, W., Zhang, C., Wu, Y., Liu, Y., Zhou, X."Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1". Molecular Medicine Reports 13, no. 6 (2016): 4569-4576. https://doi.org/10.3892/mmr.2016.5137
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