慢性牙周炎中肿瘤坏死因子ɑ对骨髓间充质干细胞成骨分化的调控作用

doi:10.7518/hxkq.2017.03.019

摘要/Abstract

摘要： 骨髓间充质干细胞（BMSCs）在重构牙周组织结构和功能、促进牙周炎好转乃至愈合方面发挥重要作用,因此BMSCs的特性尤其是其成骨分化的调控机制是目前的研究热点。肿瘤坏死因子α（TNF-α）是牙周组织炎症微环境中的主要促炎因子,与BMSCs的成骨分化密切相关。探究TNF-α调控BMSCs成骨分化的机制有助于明确牙周炎的发病机制,寻找牙周疾病新的治疗靶点,改善牙周炎的治疗效果。本文将针对TNF-α在牙周炎发生发展过程中发挥的重要作用尤其是调控BMSCs成骨分化的可能机制作一综述。

关键词: 慢性牙周炎, 肿瘤坏死因子α, 骨髓间充质干细胞, 成骨分化

Abstract: Bone marrow mesenchymal stem cells (BMSCs) and ideal adult stem cells for alveolar bone regeneration consi-derably help restore the structure and function of the periodontium and promote the healing of periodontal disease. Thus, BMSC features, especially the mechanism of osteogenic differentiation, has recently become a research hotspot. Tumor necrosis factor-α(TNF-α), which is the main factor in the periodontal inflammatory microenvironment, is directly related to the osteogenic differentiation of BMSCs. Exploring the TNF-α-regulated differentiation mechanism of BMSCs aids in the search for new treatment targets. Such investigation also promotes the development of stem cell therapy for periodontal diseases. This article aims to describe the potential of TNF-α in regulating the osteogenic differentiation of stem cells.

Key words: chronic periodontitis, tumor necrosis factor-α, bone marrow mesenchymal stem cells, osteogenic diffe-rentiation

中图分类号:

Q257

李晓光, 王一珠, 郭斌. 慢性牙周炎中肿瘤坏死因子ɑ对骨髓间充质干细胞成骨分化的调控作用[J]. 华西口腔医学杂志, 2017, 35(3): 334-338.

Li Xiaoguang, Wang Yizhu, Guo Bin.. Tumor necrosis factor-α regulates the osteogenic differentiation of bone marrow mesenchymal stem cells in chronic periodontitis[J]. West China Journal of Stomatology, 2017, 35(3): 334-338.

参考文献

[1] Cekici A, Kantarci A, Hasturk H, et al. Inflammatory and immune pathways in the pathogenesis of periodontal disease[J]. Periodontol 2000, 2014, 64(1):57-80.
[2] Bouvet-Gerbettaz S, Boukhechba F, Balaguer T, et al. Adap-tive immune response inhibits ectopic mature bone forma-tion induced by BMSCs/BCP/plasma composite in immune-competent mice[J]. Tissue Eng Part A, 2014, 20(21/22):2950-2962.
[3] Li D, Wang C, Chi C, et al. Bone marrow mesenchymal stem cells inhibit lipopolysaccharide-induced inflamma-tory reactions in macrophages and endothelial cells[J]. Me-diators Inflamm, 2016, 2016:2631439.
[4] Kaigler D, Cirelli JA, Giannobile WV. Growth factor deli-very for oral and periodontal tissue engineering[J]. Expert Opin Drug Deliv, 2006, 3(5):647-662.
[5] Auletta JJ, Deans RJ, Bartholomew AM. Emerging roles for multipotent, bone marrow-derived stromal cells in host defense[J]. Blood, 2012, 119(8):1801-1809.
[6] Zhang J, Li ZG, Si YM, et al. The difference on the osteoge-nic differentiation between periodontal ligament stem cells and bone marrow mesenchymal stem cells under inflam-matory microenviroments[J]. Differentiation, 2014, 88(4/5):97-105.
[7] Park SI, Kang SJ, Han CH, et al. The effects of topical app-lication of polycal (a 2:98 (g/g) mixture of polycan and cal-cium gluconate) on experimental periodontitis and alveolar bone loss in rats[J]. Molecules, 2016, 21(4):527.
[8] Tan J, Zhou L, Xue P, et al. Tumor necrosis factor-alpha attenuates the osteogenic differentiation capacity of perio-dontal ligament stem cells by activating protein kinase like endoplasmic reticulum kinase signaling[J]. J Periodontol, 2016, 87(8):1-22.
[9] Nanes MS. Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal pathology[J]. Gene, 2003, 321:1-15.
[10] Assuma R, Oates T, Cochran D, et al. IL-1 and TNF anta-gonists inhibit the inflammatory response and bone loss in experimental periodontitis[J]. J Immunol, 1998, 160(1):403-409.
[11] Chabaud M, Miossec P. The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflam-mation and bone resorption in an ex vivo model[J]. Arthritis Rheum, 2001, 44(6):1293-1303.
[12] Kagiya T, Nakamura S. Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast diffe-rentiation[J]. J Periodontal Res, 2013, 48(3):373-385.
[13] Li Q, Ye Z, Wen J, et al. Gelsolin, but not its cleavage, is required for TNF-induced ROS generation and apoptosis in MCF-7 cells[J]. Biochem Biophys Res Commun, 2009, 385(2):284-289.
[14] Burgess TL, Qian Y, Kaufman S, et al. The ligand for osteo-protegerin (OPGL) directly activates mature osteoclasts[J]. J Cell Biol, 1999, 145(3):527-538.
[15] Abbas S, Zhang YH, Clohisy JC, et al. Tumor necrosis factor-alpha inhibits pre-osteoblast differentiation through its type-1 receptor[J]. Cytokine, 2003, 22(1/2):33-41.
[16] Cao X, Lin W, Liang C, et al. Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-кB signaling pathway[J]. Immunol Res, 2015, 62(3):357-367.
[17] Chang J, Wang Z, Tang E, et al. Inhibition of osteoblastic bone formation by nuclear factor-kappaB[J]. Nat Med, 2009, 15(6):682-689.
[18] Gustafson B, Smith U. Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes[J]. J Biol Chem, 2006, 281(14):9507-9516.
[19] Gerstenfeld LC, Cho TJ, Kon T, et al. Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption[J]. J Bone Miner Res, 2003, 18(9):1584-1592.
[20] Ishitani T, Kishida S, Hyodo-Miura J, et al. The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5ɑ/Ca 2+ pathway to antagonize Wnt/beta-catenin sig-naling[J]. Mol Cell Biol, 2003, 23(1):131-139.
[21] Sethi JK, Vidal-Puig A. Wnt signalling and the control of cellular metabolism[J]. Biochem J, 2010, 427(1):1-17.
[22] Takada I, Mihara M, Suzawa M, et al. A histone lysine me-thyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation[J]. Nat Cell Biol, 2007, 9(11):1273-1285.
[23] Chen JR, Lazarenko OP, Shankar K, et al. A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of Wnt/beta-catenin signaling[J]. J Bone Miner Res, 2010, 25(5):1117-1127.
[24] Chen Y, Chen L, Yin Q, et al. Reciprocal interferences of TNF-α and Wnt1/β-catenin signaling axes shift bone marrow-derived stem cells towards osteoblast lineage after ethanol exposure[J]. Cell Physiol Biochem, 2013, 32(3):755-765.
[25] Verras M, Papandreou I, Lim AL, et al. Tumor hypoxia blocks Wnt processing and secretion through the induction of endop-lasmic reticulum stress[J]. Mol Cell Biol, 2008, 28(23):7212-7224.
[26] Malysheva K, de Rooij K, Lowik CW, et al. Interleukin 6/Wnt interactions in rheumatoid arthritis: interleukin 6 inhibits Wnt signaling in synovial fibroblasts and osteoblasts[J]. Croat Med J, 2016, 57(2):89-98.
[27] Qi J, Hu KS, Yang HL. Roles of TNF-α, GSK-3β and RANKL in the occurrence and development of diabetic osteoporosis[J]. Int J Clin Exp Pathol, 2015, 8(10):11995-12004.
[28] Orellana AM, Vasconcelos AR, Leite JA, et al. Age-related neuroinflammation and changes in AKT-GSK-3β and WNT/β-CATENIN signaling in rat hippocampus[J]. Aging (Albany NY), 2015, 7(12):1094-1111.
[29] Kong X, Liu Y, Ye R, et al. GSK3β is a checkpoint for TNF-α-mediated impaired osteogenic differentiation of mesen-chymal stem cells in inflammatory microenvironments[J]. Biochim Biophys Acta, 2013, 1830(11):5119-5129.
[30] Liu N, Shi S, Deng M, et al. High levels of β-catenin signa-ling reduce osteogenic differentiation of stem cells in inflam-matory microenvironments through inhibition of the nonca-nonical Wnt pathway[J]. J Bone Miner Res, 2011, 26(9):2082-2095.
[31] Han P, Lloyd T, Chen Z, et al. Proinflammatory cytokines regulate cementogenic differentiation of periodontal ligament cells by Wnt/Ca(2+) signaling pathway[J]. J Interferon Cyto-kine Res, 2016, 36(5):328-337.
[32] Mukai T, Otsuka F, Otani H, et al. TNF-alpha inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling[J]. Biochem Biophys Res Commun, 2007, 356(4):1004-1010.
[33] Lu Z, Wang G, Dunstan CR, et al. Activation and promotion of adipose stem cells by tumour necrosis factor-α precondi-tioning for bone regeneration[J]. J Cell Physiol, 2013, 228(8):1737-1744.
[34] Wang YW, Xu DP, Liu Y, et al. The effect of tumor necrosis factor-α at different concentrations on osteogenetic differen-tiation of bone marrow mesenchymal stem cells[J]. J Cranio-fac Surg, 2015, 26(7):2081-2085.
[35] Eliseev RA, Schwarz EM, Zuscik MJ, et al. Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NF-kappaB[J]. Exp Cell Res, 2006, 312(1):40-50.
[36] Yamazaki M, Fukushima H, Shin M, et al. Tumor necrosis factor alpha represses bone morphogenetic protein (BMP) signaling by interfering with the DNA binding of Smads through the activation of NF-kappaB[J]. J Biol Chem, 2009, 284(51):35987-35995.
[37] Lu X, Gilbert L, He X, et al. Transcriptional regulation of the osterix (Osx, Sp7) promoter by tumor necrosis factor identifies disparate effects of mitogen-activated protein kinase and NF kappa B pathways[J]. J Biol Chem, 2006, 281(10):6297-6306.
[38] He L, Yang N, Isales CM, et al. Glucocorticoid-induced leucine zipper (GILZ) antagonizes TNF-α inhibition of me-senchymal stem cell osteogenic differentiation[J]. PLoS One, 2012, 7(3):e31717.
[39] Shi Y, Xia YY, Wang L, et al. Neural cell adhesion molecule modulates mesenchymal stromal cell migration via activation of MAPK/ERK signaling[J]. Exp Cell Res, 2012, 318(17):2257-2267.
[40] Hah YS, Kang HG, Cho HY, et al. JNK signaling plays an important role in the effects of TNF-α and IL-1β on in vitro osteoblastic differentiation of cultured human periosteal-derived cells[J]. Mol Biol Rep, 2013, 40(8):4869-4881.
[41] Kim VN. MicroRNA biogenesis: coordinated cropping and dicing[J]. Nat Rev Mol Cell Biol, 2005, 6(5):376-385.
[42] Perri R, Nares S, Zhang S, et al. MicroRNA modulation in obesity and periodontitis[J]. J Dent Res, 2012, 91(1):33-38.
[43] Wu T, Xie M, Wang X, et al. miR-155 modulates TNF-α-inhibited osteogenic differentiation by targeting SOCS1 expression[J]. Bone, 2012, 51(3):498-505.
[44] Lee YH, Na HS, Jeong SY, et al. Comparison of inflam-matory microRNA expression in healthy and periodontitis tissues[J]. Biocell, 2011, 35(2):43-49.
[45] Li H, Li T, Wang S, et al. miR-17-5p and miR-106a are in-volved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells[J]. Stem Cell Res, 2013, 10(3):313-324.