Browse > Article
http://dx.doi.org/10.5395/rde.2019.44.e17

Effects of the cathepsin K inhibitor with mineral trioxide aggregate cements on osteoclastic activity  

Kim, Hee-Sun (Department of Conservative Dentistry, Seoul Metropolitan Governance-Seoul National University Boramae Medical Center)
Kim, Soojung (Department of Conservative Dentistry, University of Ulsan, Asan Medical Center)
Ko, Hyunjung (Department of Conservative Dentistry, University of Ulsan, Asan Medical Center)
Song, Minju (Department of Conservative Dentistry, College of Dentistry, Dankook University)
Kim, Miri (Department of Conservative Dentistry, University of Ulsan, Asan Medical Center)
Publication Information
Restorative Dentistry and Endodontics / v.44, no.2, 2019 , pp. 17.1-17.10 More about this Journal
Abstract
Objectives: Root resorption is an unexpected complication after replantation procedures. Combining anti-osteoclastic medicaments with retrograde root filling materials may avert this resorptive activity. The purpose of this study was to assess effects of a cathepsin K inhibitor with calcium silicate-based cements on osteoclastic activity. Methods: MC3T3-E1 cells were cultured for biocompatibility analyses. RAW 264.7 cells were cultured in the presence of the receptor activator of nuclear factor-kappa B and lipopolysaccharide, followed by treatment with Biodentine (BIOD) or ProRoot MTA with or without medicaments (Odanacatib [ODN], a cathepsin inhibitor and alendronate, a bisphosphonate). After drug treatment, the cell counting kit-8 assay and Alizarin red staining were performed to evaluate biocompatibility in MC3T3-E1 cells. Reverse-transcription polymerase chain reaction, tartrate-resistant acid phosphatase (TRAP) staining and enzyme-linked immunosorbent assays were performed in RAW 264.7 cells to determine the expression levels of inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and prostaglandin E2 (PGE2). Data were analyzed by one-way analysis of variance and Tukey's post hoc test (p < 0.05). Results: Biocompatibility results showed that there were no significant differences among any of the groups. RAW 264.7 cells treated with BIOD and ODN showed the lowest levels of $TNF-{\alpha}$ and PGE2. Treatments with BIOD + ODN were more potent suppressors of inflammatory cytokine expression (p < 0.05). Conclusion: The cathepsin K inhibitor with calcium silicate-based cement inhibits osteoclastic activity. This may have clinical application in preventing inflammatory root resorption in replanted teeth.
Keywords
Cathepsin K; Osteoclastogenesis; Osteoclast; Osteoblast; Root resorption;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol 2008;79:1569-1576.   DOI
2 Bar-Shavit Z. Taking a toll on the bones: regulation of bone metabolism by innate immune regulators. Autoimmunity 2008;41:195-203.   DOI
3 Yamaza T, Goto T, Kamiya T, Kobayashi Y, Sakai H, Tanaka T. Study of immunoelectron microscopic localization of cathepsin K in osteoclasts and other bone cells in the mouse femur. Bone 1998;23:499-509.   DOI
4 Kamolmatyakul S, Chen W, Yang S, Abe Y, Moroi R, Ashique AM, Li YP. IL-$1{\alpha}$ stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-$NF-{\kappa}B$ pathway. J Dent Res 2004;83:791-796.   DOI
5 Kim S, Shin SJ, Park JW, Kim S, Hwang S, Kim KH, Chung CJ. Long-term stability of autotransplanted premolars as a substitute for molars in adults. J Endod 2016;42:1286-1290.   DOI
6 Machado LA, do Nascimento RR, Ferreira DM, Mattos CT, Vilella OV. Long-term prognosis of tooth autotransplantation: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2016;45:610-617.   DOI
7 Arana-Chavez VE, Bradaschia-Correa V. Clastic cells: mineralized tissue resorption in health and disease. Int J Biochem Cell Biol 2009;41:446-450.   DOI
8 Torabinejad M, Pitt Ford TR. Root end filling materials: a review. Endod Dent Traumatol 1996;12:161-178.   DOI
9 Tsesis I, Rosen E, Taschieri S, Telishevsky Strauss Y, Ceresoli V, Del Fabbro M. Outcomes of surgical endodontic treatment performed by a modern technique: an updated meta-analysis of the literature. J Endod 2013;39:332-339.   DOI
10 Jiang J, Li H, Fahid FS, Filbert E, Safavi KE, Spangberg LS, Zhu Q. Quantitative analysis of osteoclast-specific gene markers stimulated by lipopolysaccharide. J Endod 2006;32:742-746.   DOI
11 Hung CJ, Kao CT, Chen YJ, Shie MY, Huang TH. Antiosteoclastogenic activity of silicate-based materials antagonizing receptor activator for nuclear factor kappaB ligand-induced osteoclast differentiation of murine marcophages. J Endod 2013;39:1557-1561.   DOI
12 Sasaki T, Shimizu T, Watanabe C, Hiyoshi Y. Cellular roles in physiological root resorption of deciduous teeth in the cat. J Dent Res 1990;69:67-74.   DOI
13 Hammarstrom L, Lindskog S. General morphological aspects of resorption of teeth and alveolar bone. Int Endod J 1985;18:93-108.   DOI
14 Hashiguchi D, Fukushima H, Yasuda H, Masuda W, Tomikawa M, Morikawa K, Maki K, Jimi E. Mineral trioxide aggregate inhibits osteoclastic bone resorption. J Dent Res 2011;90:912-917.   DOI
15 Komatsu K, Shimada A, Shibata T, Shimoda S, Oida S, Kawasaki K, Nifuji A. Long-term effects of local pretreatment with alendronate on healing of replanted rat teeth. J Periodontal Res 2008;43:194-200.   DOI
16 Choi SC, Kwon YD, Kim KC, Kim GT. The effects of topical application of bisphosphonates on replanted rat molars. Dent Traumatol 2010;26:476-480.   DOI
17 Leung P, Pickarski M, Zhuo Y, Masarachia PJ, Duong LT. The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone 2011;49:623-635.   DOI
18 Makras P, Delaroudis S, Anastasilakis AD. Novel therapies for osteoporosis. Metabolism 2015;64:1199-1214.   DOI
19 Hao L, Chen W, McConnell M, Zhu Z, Li S, Reddy M, Eleazer PD, Wang M, Li YP. A small molecule, odanacatib, inhibits inflammation and bone loss caused by endodontic disease. Infect Immun 2015;83:1235-1245.   DOI
20 Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet 2011;377:1276-1287.   DOI
21 Yang W, Ko H, Kim H, Kim M. The effect of cathepsin K inhibitor on osteoclastic activity compared to alendronate and enamel matrix protein. Dent Traumatol 2015;31:202-208.   DOI
22 Zhan X, Zhang C, Dissanayaka WL, Cheung GS, Jin L, Yang Y, Yan F, Tong EH. Storage media enhance osteoclastogenic potential of human periodontal ligament cells via RANKL-independent signaling. Dent Traumatol 2013;29:59-65.   DOI
23 Palokangas H, Mulari M, Vaananen HK. Endocytic pathway from the basal plasma membrane to the ruffled border membrane in bone-resorbing osteoclasts. J Cell Sci 1997;110:1767-1780.   DOI
24 Uematsu S, Mogi M, Deguchi T. Interleukin (IL)-$1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$, epidermal growth factor, and ${\beta}2$-microglobulin levels are elevated in gingival crevicular fluid during human orthodontic tooth movement. J Dent Res 1996;75:562-567.   DOI
25 Kiviranta R, Morko J, Uusitalo H, Aro HT, Vuorio E, Rantakokko J. Accelerated turnover of metaphyseal trabecular bone in mice overexpressing cathepsin K. J Bone Miner Res 2001;16:1444-1452.   DOI
26 Papadaki HA, Tsatsanis C, Christoforidou A, Malliaraki N, Psyllaki M, Pontikoglou C, Miliaki M, Margioris AN, Eliopoulos GD. Alendronate reduces serum $TNF{\alpha}$ and IL-$1{\beta}$, increases neutrophil counts, and improves bone mineral density and bone metabolism indices in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis. J Bone Miner Metab 2004;22:577-587.   DOI
27 Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci 2005;6:521-532.   DOI
28 Attik GN, Villat C, Hallay F, Pradelle-Plasse N, Bonnet H, Moreau K, Colon P, Grosgogeat B. In vitro biocompatibility of a dentine substitute cement on human MG63 osteoblasts cells: $Biodentine^{TM}$ versus $MTA^{(R)}$. Int Endod J 2014;47:1133-1141.   DOI
29 Ng KW, Martin TJ. New therapeutics for osteoporosis. Curr Opin Pharmacol 2014;16:58-63.   DOI
30 Martins CA, Leyhausen G, Volk J, Geurtsen W. Effects of alendronate on osteoclast formation and activity in vitro. J Endod 2015;41:45-49.   DOI
31 Daltoe MO, Paula-Silva FW, Faccioli LH, Gaton-Hernandez PM, De Rossi A, Bezerra Silva LA. Expression of mineralization markers during pulp response to biodentine and mineral trioxide aggregate. J Endod 2016;42:596-603.   DOI
32 Zaidi M, Blair HC, Moonga BS, Abe E, Huang CL. Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res 2003;18:599-609.   DOI
33 Suzuki N, Takimoto K, Kawashima N. Cathepsin K inhibitor regulates inflammation and bone destruction in experimentally induced rat periapical lesions. J Endod 2015;41:1474-1479.   DOI
34 Collin-Osdoby P, Yu X, Zheng H, Osdoby P. RANKL-mediated osteoclast formation from murine RAW 264.7 cells. Methods Mol Med 2003;80:153-166.