Journal of Prevention and Treatment for Stomatological Diseases ›› 2019, Vol. 27 ›› Issue (11): 695-702.doi: 10.12016/j.issn.2096-1456.2019.11.003

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Gene ontology analysis of the TNF signaling pathway in early orthodontic tooth movement of rats with periodontitis

MA Yao1,2,JIANG Zhaowei1,JIN Yunyi1,MIAO Qian1,ZHANG Chunxiang1,3,ZHANG Linkun1,3()   

  1. 1. Department of Stomatology, Nankai University School of Medicine, Tianjin 300071, China
    2. Center of Stomatology, Shunde Hospital of Southern Medical University, Foshan 528308, China
    3. Department of Orthodontics, Tianjin Stomatological Hospital, Tianjin 300041, China
  • Received:2019-01-25 Revised:2019-04-13 Online:2019-11-20 Published:2019-12-03
  • Contact: Linkun ZHANG E-mail:zlkxjtu@163.com

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Abstract: Objective To investigate the expression and function of the TNF signaling pathway in the early stage of orthodontic tooth movement with periodontitis and to provide evidence to study the early inflammatory response in patients with periodontitis orthodontic treatment. Methods Sixteen SD rats were randomly divided into four groups: group A--12 h of orthodontic tooth movement of the bilateral maxillary first molars in rats with periodontitis; group B--periodontitis model of the bilateral maxillary first molars without orthodontic tooth movement; group C--12 h of orthodontic tooth movement of the same teeth in rats with healthy periodontium; group D--control group without operations. The bilateral maxillary first molars and surrounding periodontal tissue of each group were collected for gene chip detection. Pathway enrichment analysis, qRT-PCR and GO (gene ontology) analysis were performed to identify differential genes involved in the TNF signaling pathway. Results Gene chip results showed that the TNF signaling pathway was significantly upregulated in group A, group B and group C (P <0.01). Among the differential genes involved in the pathway, 28 were upregulated and 5 were downregulated in group A, 12 were upregulated and 4 were downregulated in group B, and 12 were upregulated and 1 was downregulated in group C (P <0.05). The most significant GO items included "response to lipopolysaccharide", "inflammatory response", "positive regulation of NF-κB transcription factor activity", "positive regulation of NF-κB import into nucleus" and "response to hypoxia"(P <0.001). qRT-PCR results showed no significant difference in TNF-α mRNA expression in group C compared with that in group D, TNF-α was upregulated in both groups A and B (P <0.01), and mRNA expression decreased in the following order: group A > group B > group C (P <0.05). Compared with group D, the expression levels of prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 ( IL-6) in groups A, B and C were significantly upregulated (P <0.05), but the expression levels of PTGS2 and IL-6 in group A were lower than those in group B (P < 0.05). Conclusion The TNF signaling pathway is activated in the early stage of orthodontic tooth movement in rats with periodontitis. The pathway products participate in many biological processes and play an important role in the inflammatory response and bone absorption.

Key words: orthodontic tooth movement, periodontitis, rats, inflammatory response, tumor necrosis factor, NF-kB transcription factor, signaling pathway, gene ontology analysis

CLC Number: 

  • R783.5

Figure 1

Orthodontic tooth movement model of rats with periodontitis"

Figure 2

Schematic diagram of the TNF signaling pathway"

Table 2

Differential genes in group A"

基因名称属性差异倍数P
Ripk3上调1.5620.018
Ccl2上调4.3210.002
Mlkl上调1.6120.001
Casp7上调1.3250.014
Ccl12上调1.7690.019
Tnf-α上调1.7410.001
Tnfrsf1a上调1.7320.001
Ripk1上调1.4130.011
Nfkb1上调1.3620.031
Rps6ka4上调1.3420.014
Socs3上调3.5660.005
Tnfaip3上调2.5720.013
Traf1上调1.5940.001
Ifi47上调1.7280.007
Junb上调1.6330.031
Cxcl2上调12.4600.001
Cxcl1上调2.3450.042
Cxcl3上调3.8410.001
Cxcl10上调2.6130.004
Fas上调1.3370.033
Il-1b上调10.583<0.001
Il-6上调3.3060.013
Bcl3上调1.5510.010
Mmp3上调7.6860.001
Edn1上调1.816<0.001
Nod2上调1.9590.020
Ptgs2上调2.7280.036
Tnfrsf1b上调1.6990.027
Tab3下调-1.4110.013
Fos下调-1.7140.008
Vcam1下调-2.429<0.001
Birc2下调-1.3680.030
Pik3cg下调-1.7870.005

Figure 3

Establishment of the periodontitis model in rats"

Figure 4

Hierarchical clustering of differential genes"

Table 3

Differential genes in group B"

基因名称属性差异倍数P
Creb5上调1.3640.049
Ccl5上调1.6070.049
Fas上调1.3300.036
Il-18r1上调1.4020.042
Cxcl3上调3.1520.004
Cx3cl1上调1.3340.046
Traf1上调1.4060.011
Ifi47上调1.6100.016
Edn1上调1.3570.033
Sele上调1.8600.004
Il-1b上调3.9020.009
Bcl3上调1.4680.021
Mapk10下调-1.6320.027
Jun下调-1.5230.003
Fos下调-1.6480.012
Pik3ca下调-1.3040.010

Table 4

Differential genes in group C"

基因名称属性差异倍数P
Birc3上调1.6550.032
Ccl2上调2.9460.004
Ccl20上调1.9880.033
Cxcl2上调4.3010.001
Cxcl1上调2.840<0.001
Il-1b上调7.269<0.001
Il-6上调3.581<0.001
Socs3上调2.0470.012
Tnfaip3上调1.894<0.001
Mmp3上调4.9240.009
Sele上调1.5440.018
Ptgs2上调2.436<0.001
Fos下调-1.9210.017

Table 5

Gene ontology analysis of the differential genes of group A in the TNF signaling pathway"

GO条目P上调基因
对脂多糖的应答
<0.001
TNFrsf1a, TNF-α, TNFrsf1b, Ccl2, Cxcl3, Cxcl10, Cxcl1, Socs3, Junb, Fas, Ptgs2, Fas, Il-6, Il-1β, Mmp3, Nod2
炎症反应<0.001TNFrsf1b, TNF-α, TNFrsf1a, Ccl2, Ccl12, Cxcl3, Cxcl2, Cxcl10, Nfkb1, Fas, Ptgs2, Il-6, Il-1β
NF-κB转录因子活性的正调控<0.001Ripk3, Ripk1, Traf1, Nod2
对缺氧的应答<0.001TNF-α, TNFrsf1a, Ccl2, Socs3, Fas, Il-1β, Mmp3

Table 6

Gene ontology analysis of the differential genes of group B in the TNF signaling pathway"

GO条目P上调基因
对脂多糖的应答<0.001Ccl5, Fas, Cxcl3, Edn1, Il-1β, Il-6, Ptgs2
炎症反应<0.001TNF-α, Ccl5, Fas, Cxcl3, Cx3cl1, Sele, Il-1β, Il-6, Ptgs2
NF-κB进入细胞核的正调控<0.001Il-18r1, Il-1β, Ptgs2

Table 7

Gene ontology analysis of the differential genes of group C in the TNF signaling pathway"

GO条目P上调基因
炎症反应<0.001Ccl2,Ccl20,Cxcl2,Il1β,Il6,Sele,Ptgs2
中性粒细胞趋化<0.001Ccl2,Ccl20,Cxcl2,Cxcl1
对缺氧的应答<0.001Ccl2,Socs3,Mmp3

Figure 5

qRT-PCR results"

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