Abstract
Periodontal ligament (PDL) fibroblasts play critical roles in the regeneration of periodontal tissues damaged by periodontitis. Histone deacetylase inhibitors (HDIs) have been suggested to be potential tools in tissue engineering. The feasibility of using the HDI, sodium butyrate (NaB) for periodontal regeneration was examined by evaluating its effect on the osteogenic differentiation of human PDL fibroblasts and its modulation of the inflammatory responses to lipopolysaccharide (LPS). NaB did not cause significant cell death at 100 μM but promoted the expression of the osteoblast phenotype (Runx2, osterix, osteocalcin, and bone sialoprotein). NaB significantly inhibited the LPS-induced production of reactive oxygen species and the expression of pro-inflammatory cytokines (IL-1β and TNF-α). These results suggest that HDIs can offer a potential therapeutic agent for periodontal regeneration.
Similar content being viewed by others
References
Birkedal-Hansen H (1993) Role of cytokines and inflammatory mediators in tissue destruction. J Periodontal Res 28(6 Pt 2):500–510
Caffesse RG, de la Rosa M, Mota LF (2002) Regeneration of soft and hard tissue periodontal defects. Am J Dent 15(5):339–345
Chabane N, Zayed N, Afif H, Mfuna-Endam L, Benderdour M, Boileau C, Martel-Pelletier J, Pelletier JP, Duval N, Fahmi H (2008) Histone deacetylase inhibitors suppress interleukin-1beta-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Osteoarthr Cartil 16(10):1267–1274
Chapple IL, Matthews JB (2007) The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 43:160–232
de Boer J, Licht R, Bongers M, van der Klundert T, Arends R, van Blitterswijk C (2006) Inhibition of histone acetylation as a tool in bone tissue engineering. Tissue Eng 12(10):2927–2937
Isaka J, Ohazama A, Kobayashi M, Nagashima C, Takiguchi T, Kawasaki H, Tachikawa T, Hasegawa K (2001) Participation of periodontal ligament cells with regeneration of alveolar bone. J Periodontol 72(3):314–323
Jeon EJ, Lee KY, Choi NS, Lee MH, Kim HN, Jin YH, Ryoo HM, Choi JY, Yoshida M, Nishino N, Oh BC, Lee KS, Lee YH, Bae SC (2006) Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem 281(24):16502–16511
Jung HM, Song GA, Lee YK, Baek JH, Ryoo HM, Kim GS, Choung PH, Woo KM (2010) Modulation of the resorption and osteoconductivity of alpha-calcium sulfate by histone deacetylase inhibitors. Biomaterials 31(1):29–37
Karring T, Nyman S, Gottlow J, Laurell L (1993) Development of the biological concept of guided tissue regeneration––animal and human studies. Periodontol 2000 1(1):26–35
Li Y, Liu B, Zhao H, Sailhamer EA, Fukudome EY, Zhang X, Kheirbek T, Finkelstein RA, Velmahos GC, deMoya M, Hales CA, Alam HB (2009) Protective effect of suberoylanilide hydroxamic acid against LPS-induced septic shock in rodents. Shock 32(5):517–523
Melcher AH (1976) On the repair potential of periodontal tissues. J Periodontol 47(5):256–260
Park SH, Kim TI, Ku Y, Chung CP, Han SB, Yu JH, Lee SP, Kim HW, Lee HH (2008) Effect of hydroxyapatite-coated nanofibrous membrane on the responses of human periodontal ligament fibroblast. J Ceram Soc Jpn 116(1349):31–35
Pontoriero R, Lindhe J (1995) Guided tissue regeneration in the treatment of degree III furcation defects in maxillary molars. J Clin Periodontol 22(10):810–812
Rahman MM, Kukita A, Kukita T, Shobuike T, Nakamura T, Kohashi O (2003) Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages. Blood 101(9):3451–3459
Schroeder TM, Westendorf JJ (2005) Histone deacetylase inhibitors promote osteoblast maturation. J Bone Miner Res 20(12):2254–2263
Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY, Shi S (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364(9429):149–155
Yi T, Baek JH, Kim HJ, Choi MH, Seo SB, Ryoo HM, Kim GS, Woo KM (2007) Trichostatin A-mediated upregulation of p21(WAF1) contributes to osteoclast apoptosis. Exp Mol Med 39(2):213–221
Acknowledgments
This study was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A100948).
Conflict of interest
The authors report no conflicts of interest related to this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, TI., Han, JE., Jung, HM. et al. Analysis of histone deacetylase inhibitor-induced responses in human periodontal ligament fibroblasts. Biotechnol Lett 35, 129–133 (2013). https://doi.org/10.1007/s10529-012-0992-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-012-0992-6