A Novel Synthesized Sulfonamido-Based Gallate-JEZ-C As Potential Therapeutic Agents for Osteoarthritis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Jun 25

PMID 26107568

Citations 3

Authors

Shixiu Wei

Zhenhui Lu

Yunfeng Zou

Xiao Lin

Cuiwu Lin

Buming Liu

Li Zheng

Jinmin Zhao

Affiliations

Soon will be listed here.

Abstract

Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10-7 μg/ml to 6.25×10-5 μg/ml, among which the most profound response was observed with 6.25×10-6 μg/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C as a promising novel agent in the treatment of chondral and osteochondral lesions.

Citing Articles

Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway.

Liu X, Wang L, Ma C, Wang G, Zhang Y, Sun S J Orthop Surg Res. 2020; 14(1):470.

PMID: 31888697 PMC: 6936129. DOI: 10.1186/s13018-019-1529-7.

Correction: A Novel Synthesized Sulfonamido-Based Gallate-JEZ-C as Potential Therapeutic Agents for Osteoarthritis.

Wei S, Lu Z, Zou Y, Lin X, Lin C, Liu B PLoS One. 2019; 14(8):e0222154.

PMID: 31465511 PMC: 6715217. DOI: 10.1371/journal.pone.0222154.

Synthesis, Biological Evaluation, and Docking Studies of a Novel Sulfonamido-Based Gallate as Pro-Chondrogenic Agent for the Treatment of Cartilage.

Lin X, Chai L, Liu B, Chen H, Zheng L, Liu Q Molecules. 2016; 22(1).

PMID: 28025555 PMC: 6155774. DOI: 10.3390/molecules22010003.

References

Marshall O, Harley V . Molecular mechanisms of SOX9 action. Mol Genet Metab. 2000; 71(3):455-62. DOI: 10.1006/mgme.2000.3081. View

Karlsen T, Shahdadfar A, Brinchmann J . Human primary articular chondrocytes, chondroblasts-like cells, and dedifferentiated chondrocytes: differences in gene, microRNA, and protein expression and phenotype. Tissue Eng Part C Methods. 2010; 17(2):219-27. DOI: 10.1089/ten.TEC.2010.0200. View

Akiyama H . [Transcriptional regulation in chondrogenesis by Sox9]. Clin Calcium. 2011; 21(6):845-51. DOI: CliCa1106845851. View

Benya P, SHAFFER J . Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. 1982; 30(1):215-24. DOI: 10.1016/0092-8674(82)90027-7. View

Buschmann M, Grodzinsky A . A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics. J Biomech Eng. 1995; 117(2):179-92. DOI: 10.1115/1.2796000. View

Lu Z, Wei S, Wu H, Lin X, Lin C, Liu B . A novel synthesized sulfonamido-based gallic acid--LDQN-C: effects on chondrocytes growth and phenotype maintenance. Bioorg Chem. 2014; 57:99-107. DOI: 10.1016/j.bioorg.2014.09.005. View

Robinson D, Ash H, Yayon A, Nevo Z, Aviezer D . Characteristics of cartilage biopsies used for autologous chondrocytes transplantation. Cell Transplant. 2001; 10(2):203-8. View

Kroes B, van den Berg A, Quarles van Ufford H, Van Dijk H, Labadie R . Anti-inflammatory activity of gallic acid. Planta Med. 1992; 58(6):499-504. DOI: 10.1055/s-2006-961535. View

Ng L, Wheatley S, Muscat G, Bowles J, Wright E, Bell D . SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev Biol. 1997; 183(1):108-21. DOI: 10.1006/dbio.1996.8487. View

10.

Kwan K, Pang M, Zhou S, Cowan S, Kong R, Pfordte T . Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: implications for function. J Cell Biol. 1997; 136(2):459-71. PMC: 2134813. DOI: 10.1083/jcb.136.2.459. View

11.

Baran W, Adamek E, Ziemianska J, Sobczak A . Effects of the presence of sulfonamides in the environment and their influence on human health. J Hazard Mater. 2011; 196:1-15. DOI: 10.1016/j.jhazmat.2011.08.082. View

12.

Nuti E, Santamaria S, Casalini F, Yamamoto K, Marinelli L, La Pietra V . Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: synthesis and biological evaluation. Eur J Med Chem. 2013; 62:379-94. DOI: 10.1016/j.ejmech.2012.12.058. View

13.

Tsuchiya H, Kitoh H, Sugiura F, Ishiguro N . Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells. Biochem Biophys Res Commun. 2003; 301(2):338-43. DOI: 10.1016/s0006-291x(02)03026-7. View

14.

Ou T, Lin M, Wu C, Lin W, Wang C . Gallic acid attenuates oleic acid-induced proliferation of vascular smooth muscle cell through regulation of AMPK-eNOS-FAS signaling. Curr Med Chem. 2013; 20(31):3944-53. DOI: 10.2174/09298673113209990175. View

15.

Ishiguro N, Ito T, Ito H, Iwata H, Jugessur H, Ionescu M . Relationship of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover: analyses of synovial fluid from patients with osteoarthritis. Arthritis Rheum. 1999; 42(1):129-36. DOI: 10.1002/1529-0131(199901)42:1<129::AID-ANR16>3.0.CO;2-4. View

16.

Qin J, Liu Y, Liu J, Li J, Tan Y, Li X . Effect of Angelica sinensis Polysaccharides on Osteoarthritis In Vivo and In Vitro: A Possible Mechanism to Promote Proteoglycans Synthesis. Evid Based Complement Alternat Med. 2013; 2013:794761. PMC: 3687727. DOI: 10.1155/2013/794761. View

17.

Hsiang C, Hseu Y, Chang Y, Kumar K, Ho T, Yang H . Toona sinensis and its major bioactive compound gallic acid inhibit LPS-induced inflammation in nuclear factor-κB transgenic mice as evaluated by in vivo bioluminescence imaging. Food Chem. 2012; 136(2):426-34. DOI: 10.1016/j.foodchem.2012.08.009. View

18.

Hardy M, Seibert K, Manning P, Currie M, Woerner B, Edwards D . Cyclooxygenase 2-dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants. Arthritis Rheum. 2002; 46(7):1789-803. DOI: 10.1002/art.10356. View

19.

Andriamanalijaona R, Kypriotou M, Bauge C, Renard E, Legendre F, Raoudi M . Comparative effects of 2 antioxidants, selenomethionine and epigallocatechin-gallate, on catabolic and anabolic gene expression of articular chondrocytes. J Rheumatol. 2005; 32(10):1958-67. View

20.

Xu G, Lu Z, Lin X, Lin C, Zheng L, Zhao J . Effect of JJYMD-C, a novel synthetic derivative of gallic acid, on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro. Braz J Med Biol Res. 2014; 47(8):637-45. PMC: 4165290. DOI: 10.1590/1414-431x20143935. View