miR-146a Induces Differentiation of Periodontal Ligament Cells

Abstract

Differentiation of periodontal ligament (PDL) cells occurs under specific induction; furthermore, NF-κB signaling is important for regulation of bone differentiation. MicroRNAs are small non-coding RNAs that repress the translation of target genes and modulate cellular processes. miR-146a has been reported to modulate NF-κB signaling. This study hypothesized that miR-146a has a regulatory role in PDL differentiation by affecting NF-κB signaling. Immortalized PDL (I-PDL) cell lines were established by exogenous telomerase expression. The genesis of alkaline phosphatase and the up-regulation of miR-146a were induced by ascorbic acid in the I-PDL cells and primary PDL cells. I-PDL cells with exogenous miR-146a expression showed attenuation of NF-κB activity and exhibited higher differentiation relative to the controls. Exogenous NF-κB expression decreased the expression of differentiation markers, while the inactivation of endogenous NF-κB increased alkaline phosphatase in I-PDL cells. This study concludes that miR-146a promotes the differentiation in PDL cells through the down-regulation of NF-κB signaling.

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References

Adams AM, Soames JV, Searle RF (1993). Cultural and morphological characteristics of human periodontal ligament cells in vitro. Arch Oral Biol 38:657–662.

Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297.

Belibasakis GN, Bostanci N, Hashim A, Johansson A, Aduse-Opoku J, Curtis MA, et al. (2007). Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arggingipains. Microb Pathog 43:46–53.

Chang KW, Liu CJ, Chu TH, Cheng HW, Hung PS, Hu WY, et al. (2008). Association between high miR-211 microRNA expression and the poor prognosis of oral carcinoma. J Dent Res 87:1063–1068.

de Vries TJ, Schoenmaker T, Wattanaroonwong N, van den Hoonaard M, Nieuwenhuijse A, Beertsen W, et al. (2006). Gingival fibroblasts are better at inhibiting osteoclast formation than periodontal ligament fibroblasts. J Cell Biochem 98:370–382.

Fujii S, Maeda H, Wada N, Kano Y, Akamine A (2006). Establishing and characterizing human periodontal ligament fibroblasts immortalized by SV40T-antigen and hTERT gene transfer. Cell Tissue Res 324:117–125.

Fujita T, Otsuka-Tanaka Y, Tahara H, Ide T, Abiko Y, Mega J (2005). Establishment of immortalized clonal cells derived from periodontal ligament cells by induction of the hTERT gene. J Oral Sci 47:177–184.

Gilmore TD (2006). Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 25:6680–6684.

Hess K, Ushmorov A, Fiedler J, Brenner RE, Wirth T (2009). TNFalpha promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-kappaB signaling pathway. Bone 45:367–376.

10.

Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL (2000). The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 15:2–12.

11.

Hung PS, Kao SY, Shih YH, Chiou SH, Liu CJ, Chang KW, et al. (2008). Insulin-like growth factor binding protein-5 (IGFBP-5) suppresses the tumourigenesis of head and neck squamous cell carcinoma. J Pathol 214:368–376.

12.

Ishikawa S, Iwasaki K, Komaki M, Ishikawa I (2004). Role of ascorbic acid in periodontal ligament cell differentiation. J Periodontol 75:709–716.

13.

Kamata N, Fujimoto R, Tomonari M, Taki M, Nagayama M, Yasumoto S (2004). Immortalization of human dental papilla, dental pulp, periodontal ligament cells and gingival fibroblasts by telomerase reverse transcriptase. J Oral Pathol Med 33:417–423.

14.

Kanzaki H, Chiba M, Shimizu Y, Mitani H (2001). Dual regulation of osteoclast differentiation by periodontal ligament cells through RANKL stimulation and OPG inhibition. J Dent Res 80:887–891.

15.

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. (2005). Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773.

16.

Lin SC, Lu SY, Lee SY, Lin CY, Chen CH, Chang KW (2005). Areca (betel) nut extract activates mitogen-activated protein kinases and NF-kappaB in oral keratinocytes. Int J Cancer 116:526–535.

17.

Liu WK, Yen PF, Chien CY, Fann MJ, Su JY, Chou CK (2004). The inhibitor ABIN-2 disrupts the interaction of receptor-interacting protein with the kinase subunit IKKgamma to block activation of the transcription factor NF-kappaB and potentiate apoptosis. Biochem J 378(Pt 3):867–876.

18.

Nemoto E, Honda T, Kanaya S, Takada H, Shimauchi H (2008). Expression of functional Toll-like receptors and nucleotide-binding oligomerization domain proteins in murine cementoblasts and their upregulation during cell differentiation. J Periodontal Res 43:585–593.

19.

Pi SH, Lee SK, Hwang YS, Choi MG, Lee SK, Kim EC (2007). Differential expression of periodontal ligament-specific markers and osteogenic differentiation in human papilloma virus 16-immortalized human gingival fibroblasts and periodontal ligament cells. J Periodontal Res 42:104–113.

20.

Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al. (2004). Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155.

21.

Shimono M, Ishikawa T, Ishikawa H, Matsuzaki H, Hashimoto S, Muramatsu T, et al. (2003). Regulatory mechanisms of periodontal regeneration. Microsc Res Tech 60:491–502.

22.

Shivdasani RA (2006). MicroRNAs: regulators of gene expression and cell differentiation. Blood 108:3646–3653.

23.

Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006). NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486.

24.

Taganov KD, Boldin MP, Baltimore D (2007). MicroRNAs and immunity: tiny players in a big field. Immunity 26:133–137.

25.

Tseng YH, Chang KW, Liu CJ, Lin CY, Yang SC, Lin SC (2008). Areca nut extract represses migration and differentiation while activating matrix metalloproteinase-9 of normal gingival epithelial cells. J Periodontal Res 43:490–499.

26.

Walsh MC, Choi Y (2003). Biology of the TRANCE axis. Cytokine Growth Factor Rev 14:251–263.

27.

Yamaguchi M, Aihara N, Kojima T, Kasai K (2006). RANKL increase in compressed periodontal ligament cells from root resorption. J Dent Res 85:751–756.

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