Intra-articular Treatment with Triamcinolone Hexacetonide Associated with Gold Nanoparticles Reduces Cartilage Degeneration in an Animal Model of Osteoarthritis

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Abstract

Introduction: The association between triamcinolone hexacetonide (TH) and gold nanoparticles (GNPs) represents a promising treatment due to the potential anti-inflammatory and antioxidant effects of these compounds. In this study, we evaluated the effects of intra-articular treatment of TH associated with GNPs in a mechanical model of osteoarthritis (OA).

Methods: Fifty Wistar rats were divided into five groups: Sham; OA; OA+TH; OA+GNPs; OA+TH-GNPs. Both applications were performed 30 and 60 days after the model was induced. After 30 days of the last application, the animals were euthanized.

Results: Only the combined treatment with TH and GNPs promoted a reduction in proinflammatory cytokines and an increase in anti-inflammatory cytokines. The OA+TH-GNPs group obtained a significant reduction in the production of oxidants and oxidative damage markers while an increase in antioxidants. Histologically, all treated groups showed results of a significant increase in cartilage thickness and chondrocyte count, the OA+TH-GNPs group had similar behavior to the group without osteoarthritis, with significantly smaller amounts of chondrocytes than the OA group.

Conclusion: The intra-articular use of TH associated with GNPs may be able to prevent the progression of the pathology and minimize joint degradation.

Graphical Abstract

[1]
Ríos M, Foretz M, Viollet B, et al. Lipoprotein internalisation induced by oncogenic AMPK activation is essential to maintain glioblastoma cell growth. Eur J Cancer 2014; 50(18): 3187-97.
[http://dx.doi.org/10.1016/j.ejca.2014.09.014] [PMID: 25450947]
[2]
Green A, Engstrom C, Friis PJMJA. Exercise: an essential evidence-based medicine. Med J Aust 2018; 208(6): 242-3.2018.
[http://dx.doi.org/10.5694/mja18.00033]
[3]
Pritzker KP, Gay S, Jimenez S, et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage 2006; 14(1): 13-29.
[http://dx.doi.org/10.1016/j.joca.2005.07.014]
[4]
Henrotin Y, Kurz B, Aigner TJO. Oxygen and reactive oxygen species in cartilage degradation: friends or foes? Osteoarthritis Cartilage 2005; 13(8): 643-54.
[5]
Li D, Wang W. Reactive oxygen species: the 2-edged sword of osteoarthritis. Am J Med Sci 2012; 344(6): 486-90.
[6]
Zahan OM, Serban O, Gherman C, Fodor DJM. The evaluation of oxidative stress in osteoarthritis. Med Pharm Rep 2020; 93(1): 12-22.
[7]
Turrens J-F. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552(Pt 2): 335-44.
[8]
Gomez MA, Griffin MA, Jindal S, Rule KD, Cooper VR. The effect of octahedral tilting on proton binding sites and transition states in pseudo-cubic perovskite oxides. J Chem Phys 2005; 123(9): 094703.
[http://dx.doi.org/10.1063/1.2035099] [PMID: 16164358]
[9]
Drevet S, Gavazzi G, Grange L, Dupuy C. Reactive oxygen species and NADPH oxidase 4 involvement in osteoarthritis. Exp Gerontol 2018; 1(111): 107-17.
[10]
Wilusz RE, Sanchez-Adams J. The structure and function of the pericellular matrix of articular cartilage. Matrix Biol 2014; 39: 25-32.
[11]
Heinemeier KM, Schjerling P, Heinemeier J, et al. Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage. Sci Transl Med 2016; 8(346): 346ra90.
[http://dx.doi.org/10.1126/scitranslmed.aad8335]
[12]
Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 2012; 64(4): 465-74.
[http://dx.doi.org/10.1002/acr.21596]
[13]
Joosten E, van den Berg A, Riezler R, et al. Metabolic evidence that deficiencies of vitamin B− 12 (cobalamin), folate, and vitamin B− 6 occur commonly in elderly people. Am J Clin Nutr 1993; 58(4): 468-76.
[14]
Scherer J, Rainsford K, Kean CA, Kean WFJI. Pharmacology of intra-articular triamcinolone. Inflammopharmacology 2014; 22(4): 201-17.
[http://dx.doi.org/10.1007/s10787-014-0205-0]
[15]
Lawson TB, Mäkelä JT, Klein T, Snyder BD. Nanotechnology and Osteoarthritis. Part 2: Opportunities for advanced devices and therapeutics. J Orthop Res 2021; 39(3): 473-84.
[16]
Aminabad NS, Farshbaf M. Recent advances of gold nanoparticles in biomedical applications: state of the art. Cell Biochem Biophys 2019; 77(2): 123-37.
[17]
Wu Q, Wang K, Wang X, Liang G. Delivering siRNA to control osteogenic differentiation and real-time detection of cell differentiation in human mesenchymal stem cells using multifunctional gold nanoparticles. J Mater Chem B 2020; 8(15): 3016-27.
[18]
Filho MCB, Dos Santos Haupenthal DP, Zaccaron RP, et al. Intra-articular treatment with hyaluronic acid associated with gold nanoparticles in a mechanical osteoarthritis model in Wistar rats. J Orthop Res 2021; 39(12): 2546-55.
[http://dx.doi.org/10.1002/jor.25008]
[19]
Insall J. A midline approach to the knee. J Bone Joint Surg Am 1971; 53(8): 1584-6.
[20]
Vechia ICD, Steiner BT, Freitas ML, et al. Comparative cytotoxic effect of citrate-capped gold nanoparticles with different sizes on noncancerous and cancerous cell lines. J Nanopart Res 2020; 22: 133.
[http://dx.doi.org/10.1007/s11051-020-04839-1]
[21]
Moscardi LC, Espíndola TP, Ferreira AA, et al. Lasertherapy as a strategy for treatment healing under caloric restriction-study in rats. J Pharm Pharmacol 2018; 6: 647-58.
[22]
Andrade TAM, Masson-Meyers DS, Caetano GF, et al. Skin changes in streptozotocin-induced diabetic rats. Biochem Biophys Res Commun 2017; 490(4): 1154-61.2017.
[http://dx.doi.org/10.1016/j.bbrc.2017.06.166]
[23]
Mendes C, dos Santos Haupenthal DP, Zaccaron RP, et al. Effects of the association between photobiomodulation and hyaluronic acid linked gold nanoparticles in wound healing. ACS Biomater Sci Eng 2020; 6(9): 5132-44.
[http://dx.doi.org/10.1021/acsbiomaterials.0c00294]
[24]
Bannister JV, Calabrese L. Assays for superoxide dismutase. Methods Biochem Anal 1987; 32: 279-312.
[PMID: 3033431]
[25]
Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[26]
García-Millán E, Quintáns-Carballo M, Otero-Espinar FJ. Improved release of triamcinolone acetonide from medicated soft contact lenses loaded with drug nanosuspensions. Int J Pharm 2017; 525(1): 226-36.
[http://dx.doi.org/10.1016/j.ijpharm.2017.03.082] [PMID: 28412447]
[27]
McAlindon TE, Bannuru RR, Sullivan M, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014; 22(3): 363-88.
[http://dx.doi.org/10.1016/j.joca.2014.01.003]
[28]
DiBattista JA, Martel-Pelletier J, Wosu LO, Sandor T, Antakly T, Pelletier JP. Glucocorticoid receptor mediated inhibition of interleukin-1 stimulated neutral metalloprotease synthesis in normal human chondrocytes. J Clin Endocrinol Metab 1991; 72(2): 316-26.
[29]
Pelletier J, Cloutier J, Martel-Pelletier JJA. In vitro effects of NSAIDs and corticosteroids on the synthesis and secretion of interleukin 1 by human osteoarthritic synovial membranes. Agents Actions Suppl 1993; 39: 181-93.
[30]
Abramoff B, Caldera FEJMC. Osteoarthritis: pathology, diagnosis, and treatment options. Med Clin North Am 2020; 104(2): 293-311.
[31]
Nixon M, Andrew R, Chapman KEJS. It takes two to tango: dimerisation of glucocorticoid receptor and its anti-inflammatory functions. Steroids 2013; 78(1): 59-68.
[http://dx.doi.org/10.1016/j.steroids.2012.09.013]
[32]
Zhang Y, Pizzute T, Pei MJTEPBR. Anti-inflammatory strategies in cartilage repair. Tissue Eng Part B Rev 2014; 20(6): 655-8.
[http://dx.doi.org/10.1089/ten.teb.2014.0014]
[33]
Jeon KI, Byun MS, Jue DM. Gold compound auranofin inhibits IκB kinase (IKK) by modifying Cys-179 of IKKβ subunit. Exp Mol Med 2003; 35(2): 61-6.
[http://dx.doi.org/10.1038/emm.2003.9] [PMID: 12754408]
[34]
Chen H, Dorrigan A, Saad S, Hare DJ, Cortie MB, Valenzuela SM. In vivo study of spherical gold nanoparticles: inflammatory effects and distribution in mice. PLoS One 2013; 8(2): e58208.
[http://dx.doi.org/10.1371/journal.pone.0058208] [PMID: 23469154]
[35]
Karthick V, Kumar VG, Dhas TS, et al. Effect of biologically synthesized gold nanoparticles on alloxan-induced diabetic rats-An in vivo approach. Colloids Surf B Biointerfaces 2014; 122: 505-11.
[36]
Pinho RA, Haupenthal DPS, Fauser PE, Thirupathi A, Silveira PCL. Gold nanoparticle-based therapy for muscle inflammation and oxidative stress. J Inflamm Res 2022; 15: 3219-34.
[http://dx.doi.org/10.2147/JIR.S327292] [PMID: 35668914]
[37]
Lepetsos P. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta 2016; 1862(4): 576-91.
[38]
Han L, Song JH, Yoon JH, et al. TNF-α and TNF-β polymorphisms are associated with susceptibility to osteoarthritis in a Korean population. J Pathol Transl Med 2012; 46(1): 30-7.
[http://dx.doi.org/10.4132/KoreanJPathol.2012.46.1.30]
[39]
Wojdasiewicz P. Poniatowski ŁA. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm 2014; 2014: 561459.
[40]
Clark ARJM. Anti-inflammatory functions of glucocorticoid-induced genes. Mol Cell Endocrinol 2007; 275(1-2): 79-97.
[41]
Coutinho AE, Chapman KEJM. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011; 335(1): 2-13.
[42]
Spies C, Strehl C. Pharmacodynamics of glucocorticoids. Clin Experimen Rheumatol 2010; 29(5) (S68): S13-8.
[43]
Davidson Blaney E, van der Kraan P, van den Berg WJOC. TGF-beta and osteoarthritis. Osteoarthritis Cartilage 2007; 15(6): 597-604.
[44]
Shen J, Li S. TGF-β signaling and the development of osteoarthritis. Bone Res 2014; 2: 14002.
[45]
van der Kraan PM. Differential role of transforming growth factor-beta in an osteoarthritic or a healthy joint. J Bone Metab 2018; 25(2): 65-72.
[46]
Marangoni VS, Paino IM, Zucolotto VJC, Biointerfaces SB. Synthesis and characterization of jacalin-gold nanoparticles conjugates as specific markers for cancer cells. Colloids Surf B Biointerfaces 2013; 112: 380-6.
[http://dx.doi.org/10.1016/j.colsurfb.2013.07.070]
[47]
Dwivedi P, Nayak V. Role of gold nanoparticles as drug delivery vehicles for chondroitin sulfate in the treatment of osteoarthritis. Biotechnol Prog 2015; 31(5): 1416-22.
[48]
Ma JS, Kim WJ, Kim JJ, et al. Gold nanoparticles attenuate LPS-induced NO production through the inhibition of NF-kappaB and IFN-beta/STAT1 pathways in RAW264.7 cells. Nitric Oxide 2010; 23(3): 214-9.
[49]
Khan MA. Nano-gold displayed anti-inflammatory property via NF-kB pathways by suppressing COX-2 activity. Artif Cells Nanomed Biotechnol 2018; 46(S1): 1149-58.
[50]
Razzaq H, Saira F, Yaqub A, Qureshi R, Mumtaz M, Saleemi S. Interaction of gold nanoparticles with free radicals and their role in enhancing the scavenging activity of ascorbic acid. J Photochem Photobiol B 2016; 161: 266-72.
[http://dx.doi.org/10.1016/j.jphotobiol.2016.04.003] [PMID: 27288656]
[51]
Goldstein A, Soroka Y. Frušić-Zlotkin M, Lewis A, Kohen RJN. The bright side of plasmonic gold nanoparticles; activation of Nrf2, the cellular protective pathway. Nanoscale 2016; 8: 11748-59.
[52]
Regan E, Bowler R, Crapo JJO. Joint fluid antioxidants are decreased in osteoarthritic joints compared to joints with macroscopically intact cartilage and subacute injury. Osteoarthritis Cartilage 2008; 16(4): 515-21.
[53]
Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016; 12(7): 412-20.
[http://dx.doi.org/10.1038/nrrheum.2016.65] [PMID: 27192932]
[54]
Pemmari A, Leppänen T, Hämäläinen M, Moilanen T, Moilanen E. Chondrocytes from osteoarthritis patients adopt distinct phenotypes in response to central TH1/TH2/TH17 cytokines. Int J Mol Sci 2021; 22(17): 9463.
[http://dx.doi.org/10.3390/ijms22179463] [PMID: 34502384]
[55]
Aigner T, Fundel K, Saas J, et al. Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum 2006; 54(11): 3533-44.
[http://dx.doi.org/10.1002/art.22174] [PMID: 17075858]
[56]
Sandy JD, Chan DD, Trevino RL, Wimmer MA, Plaas A. Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis. Osteoarthritis Cartilage 2015; 23(11): 1939-45.
[http://dx.doi.org/10.1016/j.joca.2015.03.027] [PMID: 26521740]
[57]
Hardingham T. Extracellular matrix and pathogenic mechanisms in osteoarthritis. Curr Rheumatol Rep 2008; 10(1): 30-6.
[http://dx.doi.org/10.1007/s11926-008-0006-9] [PMID: 18457609]
[58]
Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. BioMed Res Int 2013; 2013: 1-10.
[http://dx.doi.org/10.1155/2013/284873] [PMID: 24069595]