Keywords
Antimicrobial cationic peptides
Nitric oxide
Osteogenesis
How to Cite
Abstract
Aim: Several systemic diseases, such as periodontitis and apical periodontitis, can cause extensive bone resorption. Host defense peptides may have the potential for the development of novel therapies for the bone resorption process. This study evaluated the potential of host defense peptides clavanins A, MO, and LL-37 in in vitro osteoclastogenesis. Methods: RAW 264.7 cultures were stimulated with recombinant of receptor activator of nuclear factor kappa B ligand in the presence of different tested concentrations of host defense peptides, besides calcium hydroxide and doxycycline. Cellular viability, nitric oxide production, and a number of differentiated osteoclast-like cells were also evaluated. Results: Results showed that none of the substances were cytotoxic, except for 128 μg.mL-1 of doxycycline after 3 days. Host defense peptides, calcium hydroxide, and doxycycline did not interfere in nitric oxide production or downregulated it. An exception was observed in the presence of 2 μg.mL-1 of doxycycline, in which nitric oxide production was up-regulated. All host defense peptides were capable of reducing osteoclast-like cell differentiation. Conclusion: Host defense peptides clavanins A and MO demonstrated to be potential suppressors of osteoclastogenesis in vitro without interfering in cellular viability and nitric oxide production. These promising results need to be further analyzed in in vivo models of bone resorption.
References
Schett G, Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol. 2012;8(11):656-64. doi:10.1038/nrrheum.2012.153.
Park-Min KH. Mechanisms involved in normal and pathological osteoclastogenesis. Cell Mol Life Sci. 2018;75(14):2519-28. doi:10.1007/s00018-018-2817-9.
van't Hof RJ, Armour KJ, Smith LM, Armour KE, Wei XQ, Liew FY, et al. Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption. Proc Natl Acad Sci U S A. 2000;97(14):7993-8. doi:10.1073/pnas.130511497.
Kırzıoğlu FY, Özmen Ö, Doğan B, Bulut MT, Fentoğlu Ö, Özdem M. Effects of rosuvastatin on inducible nitric oxide synthase in rats with hyperlipidaemia and periodontitis. J Periodontal Res. 2018;53(2):258-66. doi:10.1111/jre.12513.
Smiley CJ, Tracy SL, Abt E, Michalowicz BS, John MT, Gunsolley J, et al. Evidence-based clinical practice guideline on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. J Am Dent Assoc. 2015;146(7):525-35. doi:10.1016/j.adaj.2015.01.026.
Figdor D. Microbial aetiology of endodontic treatment failure and pathogenic properties of selected species. Aust Endod J. 2004;30(1):11-4. doi:10.1111/j.1747-4477.2004.tb00159.x.
Gorr SU, Abdolhosseini M. Antimicrobial peptides and periodontal disease. J Clin Periodontol. 2011;38 Suppl 11:126-41. doi:10.1111/j.1600-051X.2010.01664.x.
Wimley WC. Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol. 2010;5(10):905-17. doi:10.1021/cb1001558.
Silva ON, Fensterseifer IC, Rodrigues EA, Holanda HH, Novaes NR, Cunha JP, et al. Clavanin A improves outcome of complications from different bacterial infections. Antimicrob Agents Chemother. 2015;59(3):1620-6. doi:10.1128/AAC.03732-14.
Silva ON, de la Fuente-Núñez C, Haney EF, Fensterseifer IC, Ribeiro SM, Porto WF, et al. An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities. Sci Rep. 2016 Nov 2;6:35465. doi: 10.1038/srep35465.
Supanchart C, Thawanaphong S, Makeudom A, Bolscher JG, Nazmi K, Kornak U, et al. The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis. J Dent Res. 2012;91(11):1071-7. doi:10.1177/0022034512460402.
Park OJ, Kim J, Ahn KB, Lee JY, Park YJ, Kum KY, et al. A 15-amino acid C-terminal peptide of beta-defensin-3 inhibits bone resorption by inhibiting the osteoclast differentiation and disrupting podosome belt formation. J Mol Med (Berl). 2017;95(12):1315-25. doi:10.1007/s00109-017-1589-2.
L Lima SMF, Freire MS, Cantuária APC, Martins DCM, Amorim IA, Dantas EMGL, et al. The use of host defense peptides in root canal therapy in rats. Clin Oral Investig. 2020 Nov 16. doi: 10.1007/s00784-020-03684-9.
Lima SMF, Freire MS, Gomes ALO, Cantuária APC, Dutra FRP, Magalhães BS, et al. Antimicrobial and immunomodulatory activity of host defense peptides, clavanins and LL-37, in vitro: An endodontic perspective. Peptides. Sep 2017;95:16-24. doi:10.1016/j.peptides.2017.07.005.
Murphy JB, Kies MW. Note on the spectrophotometric determination of proteins in dilute solutions. Biochim Biophys Acta. 1960;45:382-4. doi: 10.1016/0006-3002(60)91464-5.
Raschke WC, Baird S, Ralph P, Nakoinz I. Functional macrophage cell lines transformed by Abelson leukemia virus. Cell. 1978;15(1):261-7. doi:10.1016/0092-8674(78)90101-0.
van de Loosdrecht AA, Nennie E, Ossenkoppele GJ, Beelen RH, Langenhuijsen MM. Cell mediated cytotoxicity against U 937 cells by human monocytes and macrophages in a modified colorimetric MTT assay. A methodological study. J Immunol Methods. 1991;141(1):15-22. doi:10.1016/0022-1759(91)90205-t.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. Oct 1982;126(1):131-8. doi:10.1016/0003-2697(82)90118-x.
Lima SMF, de Pádua GM, Sousa MGDC, Freire MS, Franco OL, Rezende TMB. Antimicrobial peptide-based treatment for endodontic infections--biotechnological innovation in endodontics. Biotechnol Adv. 2015 Jan-Feb 2015;33(1):203-13. doi:10.1016/j.biotechadv.2014.10.013.
Mandal SM, Khan J, Mahata D, Saha S, Sengupta J, Silva ON, et al. A self-assembled clavanin A-coated amniotic membrane scaffold for the prevention of biofilm formation by ocular surface fungal pathogens. Biofouling. 2017 Nov;33(10):881-891. doi: 10.1080/08927014.2017.1383400.
Wang FS, Wang CJ, Chen YJ, Huang YT, Huang HC, Chang PR, et al. Nitric oxide donor increases osteoprotegerin production and osteoclastogenesis inhibitory activity in bone marrow stromal cells from ovariectomized rats. Endocrinology. 2004;145(5):2148-56. doi:10.1210/en.2003-1074.
Vieira GHA, Messora MR, Moura JMT, Fernandes PG, Furlaneto FAC, Palioto DB, et al. Sub-antimicrobial doses of doxycycline decreased bone loss related to ligature-induced periodontitis in hypertensive rats. Arch Oral Biol. 2019;101:77-84. doi:10.1016/j.archoralbio.2019.03.011.
Guo J, Yang D, Okamura H, Teramachi J, Ochiai K, Qiu L, et al. Calcium hydroxide suppresses Porphyromonas endodontalis lipopolysaccharide-induced bone destruction. J Dent Res. 2014;93(5):508-13. doi:10.1177/0022034514526886.
Modena KC, Casas-Apayco LC, Atta MT, Costa CA, Hebling J, Sipert CR, et al. Cytotoxicity and biocompatibility of direct and indirect pulp capping materials. J Appl Oral Sci. 2009;17(6):544-54. doi:10.1590/s1678-77572009000600002.
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