Skip to main content
SpringerLink
Log in

Regulation of proliferation and apoptosis of aging periodontal ligament cells by autophagy-related gene 7

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Human periodontal ligament cells (hPDLCs) can be applied in periodontal regeneration engineering to repair the tissue defects related to periodontitis. Theoretically, it can affect the vitality of hPDLCs that cell aging increases apoptosis and decreases autophagy. Autophagy is a highly conserved degradation mechanism, which degrades the aging and damaged intracellular organelles through autophagy lysosomes to maintain normal intracellular homeostasis. Meanwhile, autophagy-related gene 7 (ATG7) is a key gene that regulates the level of cellular autophagy.

Objective

This study was to explore the effects of autophagic regulation of aging hPDLCs on cell proliferation and cell apoptosis.

Methods

A cell model of aging hPDLCs overexpressing and silencing ATG7 were respectively constructed by lentiviral vectors in vitro. A series of experiments was performed to confirm relevant senescence phenotype on aging hPDLCs, and to detect the effects of changes in autophagy on their proliferation and apoptosis-related factors in aging hPDLCs.

Results

The results showed that overexpression of ATG7 could motivate autophagy, promoting proliferation of aging hPDLCs and inhibiting apoptosis synchronously (P < 0.05). On the contrary, suppressing autophagy levels by silencing ATG7 would inhibit cell proliferation and accelerate cell senescence (P < 0.05).

Conclusion

ATG7 regulates the proliferation and apoptosis of aging hPDLCs. Hence, autophagy may act as a target to delay senescence of hPDLCs, which can be helpful in the future in-depth study on regeneration and functionalization of periodontal supporting tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. LEE E, KIM Y S, LEE Y M et al (2021) Identification of stemness and differentially expressed genes in human cementum-derived cells [J]. J periodontal implant Sci 51(5):329–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. SUN G, YANG Y, LU X et al (2019) Comparison of Periodontal Ligament Cell lines with adenovirus- and lentivirus-mediated human telomerase reverse transcription expression [J]. Hum Gene Ther Methods 30(2):53–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. KONO K, MAEDA H, FUJII S et al (2013) Exposure to transforming growth factor-β1 after basic fibroblast growth factor promotes the fibroblastic differentiation of human periodontal ligament stem/progenitor cell lines [J]. Cell Tissue Res 352(2):249–263

    Article  CAS  PubMed  Google Scholar 

  4. WANG L, SHI S, BAI R et al (2020) Biological properties of bone marrow stem cells and adipose-derived stem cells derived from T2DM rats: a comparative study [J], vol 10. Cell & bioscience, p 102

  5. MCHUGH D (2018) Senescence and aging: causes, consequences, and therapeutic avenues [J]. J Cell Biol 217(1):65–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. MUñOZ-ESPíN D, CAñAMERO M, MARAVER A et al (2013) Programmed cell senescence during mammalian embryonic development [J]. Cell 155(5):1104–1118

    Article  PubMed  Google Scholar 

  7. KUILMAN T, MICHALOGLOU C, MOOI W J et al (2010) The essence of senescence [J]. Genes Dev 24(22):2463–2479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. SALMINEN A, KAARNIRANTA K (2013) Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process [J]. Ageing Res Rev 12(2):520–534

    Article  CAS  PubMed  Google Scholar 

  9. HANSEN M, RUBINSZTEIN D C (2018) WALKER D W. Autophagy as a promoter of longevity: insights from model organisms [J]. Nat Rev Mol Cell Biol 19(9):579–593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. MIZUSHIMA N (2011) Autophagy: renovation of cells and tissues [J]. Cell 147(4):728–741

    Article  CAS  PubMed  Google Scholar 

  11. Cawthon H, Chakraborty R, Roberts JR et al (2018) Control of autophagosome size and number by Atg7[J].Biochem Biophys Res Commun. 2.651-656.

  12. CHOI S I DADAKHUJAEVS, MAENG Y S et al (2015) Disrupted cell cycle arrest and reduced proliferation in corneal fibroblasts from GCD2 patients: a potential role for altered autophagy flux [J]. Biochem Biophys Res Commun 456(1):288–293

    Article  PubMed  Google Scholar 

  13. DAI J, SUN Y, CHEN D et al (2019) Negative regulation of PI3K/AKT/mTOR axis regulates fibroblast proliferation, apoptosis and autophagy play a vital role in triptolide-induced epidural fibrosis reduction [J]. Eur J Pharmacol 864:172724

    Article  CAS  PubMed  Google Scholar 

  14. QIN R, CUI Z, ZHOU H et al (2022) Effect of lentivirus-mediated BMP2 from autologous tooth on the proliferative and osteogenic capacity of human periodontal ligament cells [J]. J Periodontal Res. https://doi.org/10.1111/jre.13025

    Article  PubMed  Google Scholar 

  15. CAO Y, YANG W TYLERMA et al (2013) Noggin attenuates cerulein-induced acute pancreatitis and impaired autophagy [J]. Pancreas 42(2):301–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. CAI B, ZHENG Y (2019) BMP2-mediated PTEN enhancement promotes differentiation of hair follicle stem cells by inducing autophagy [J]. Exp Cell Res 385(2):111647

    Article  CAS  PubMed  Google Scholar 

  17. KWON T, LAMSTER I B LEVINL (2021) Current concepts in the management of periodontitis [J]. Int Dent J 71(6):462–476

    Article  PubMed  PubMed Central  Google Scholar 

  18. TOMOKIYO A, WADA N (2019) Periodontal Ligament Stem cells: regenerative potency in periodontium [J]. Stem Cells Dev 28(15):974–985

    Article  PubMed  Google Scholar 

  19. MITSIADIS TA (2009) Cell fate determination during tooth development and regeneration [J]. Birth defects research part C, embryo today: reviews. 87(3):199–211

  20. KONG Y, CUI H (2011) Regulation of senescence in cancer and aging [J]. J Aging Res 2011:963172

    Article  PubMed  PubMed Central  Google Scholar 

  21. HE C, ZHOU C, KENNEDY B K (2018) The yeast replicative aging model [J]. Biochim Biophys Acta Mol Basis Dis 1864(9 Pt A):2690–2696

    Article  CAS  PubMed  Google Scholar 

  22. UCHIL PD, NAGARAJAN A (2017) KUMAR P. β-Galactosidase [J]. Cold Spring Harbor protocols, 2017(10): pdb.top096198

  23. KARIMIAN A, AHMADI Y (2016) Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage [J]. DNA Repair 42:63–71

    Article  CAS  PubMed  Google Scholar 

  24. DING Q, LIU H, LIU L et al (2021) Deletion of p16 accelerates fracture healing in geriatric mice [J]. Am J translational Res 13(10):11107–11125

    CAS  Google Scholar 

  25. LIPINSKI M M, ZHENG B, LU T et al (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease [J]. Proc Natl Acad Sci USA 107(32):14164–14169

    Article  PubMed  PubMed Central  Google Scholar 

  26. YANG M C, LIN R W, HUANG S, B et al (2016) Bim directly antagonizes bcl-xl in doxorubicin-induced prostate cancer cell apoptosis independently of p53 [J]. 15(3):394–402 Cell cycle (Georgetown, Tex)

  27. CHILDS B G, BAKER D J, KIRKLAND JL et al (2014) Senescence and apoptosis: dueling or complementary cell fates? [J]. EMBO Rep 15(11):1139–1153

    Article  PubMed  Google Scholar 

  28. ARGUELLES S, GUERRERO-CASTILLA A, CANO M et al (2019) Advantages and disadvantages of apoptosis in the aging process [J]. Ann N Y Acad Sci 1443(1):20–33

    Article  PubMed  Google Scholar 

  29. ZENG S, QIN X, HE X et al (2016) [Construction of human mucosa oral epithelial cell lines overexpressing telomerase reverse transcriptase gene mediated by lentivirus] [J]. Hua Xi Kou Qiang Yi Xue Za Zhi 34(5):443–447

    Google Scholar 

  30. QIN X, LU X, WANG Y et al (2020) Mechanism and significance of apoptosis of the immortalized human oral mucosal epithelial cells established by Lentivirus-mediated hTERT [J]. Mol Biol Rep 47(7):5469–5475

    Article  CAS  PubMed  Google Scholar 

  31. GLICK D, BARTH S, MACLEOD K F (2010) Autophagy: cellular and molecular mechanisms [J]. J Pathol 221(1):3–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. LIU W J YEL, HUANG W F et al (2016) p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation [J]. Cell Mol Biol Lett 21:29

    Article  PubMed  PubMed Central  Google Scholar 

  33. XU Z, TEIXEIRA M T (2019) The many types of heterogeneity in replicative senescence [J]. Yeast 36(11):637–648

    Article  PubMed  Google Scholar 

  34. WONG S Q, KUMAR A V, MILLS J et al (2020) Autophagy in aging and longevity [J]. Hum Genet 139(3):277–290

    Article  Google Scholar 

  35. KANG C, XU Q, MARTIN T D et al (2015) The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4 [J]. Science 349(6255):aaa5612

    Article  PubMed  PubMed Central  Google Scholar 

  36. WANG S, FENG R, SHI Y et al (2021) Intracellular alpha-fetoprotein interferes with all-trans retinoic acid induced ATG7 expression and autophagy in hepatocellular carcinoma cells [J]. Sci Rep 11(1):2146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. YANG Y, KARSLI-UZUNBAS G, POILLET-PEREZ L et al (2020) Autophagy promotes mammalian survival by suppressing oxidative stress and p53 [J]. Genes Dev 34(9–10):688–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. JEELANI R, CHATZICHARALAMPOUS C, KOHAN-GHADR H, R et al (2020) Hypochlorous acid reversibly inhibits caspase-3: a potential regulator of apoptosis [J]. Free Radic Res 54(1):43–56

    Article  CAS  PubMed  Google Scholar 

  39. ASADI M, TAGHIZADEH S (2022) Caspase-3: structure, function, and biotechnological aspects [J]. Biotechnol Appl Chem 69(4):1633–1645

    CAS  Google Scholar 

  40. MUKHOPADHYAY S, PANDA P K, SINHA N et al (2014) Autophagy and apoptosis: where do they meet? [J]. Apoptosis 19(4):555–566

    Article  CAS  PubMed  Google Scholar 

  41. GUI F, YU X, WU Y et al (2022) Mechanism of LncHOTAIR regulating proliferation, apoptosis, and Autophagy of Lymphoma cells through hsa-miR-6511b-5p/ATG7 Axis. Evidence-based Complement Altern medicine: eCAM 2022:2166605

    Article  Google Scholar 

  42. WANG J, THOMAS H R, LI Z et al (2021) Puma, noxa, p53, and p63 differentially mediate stress pathway induced apoptosis [J]. Cell Death Dis 12(7):659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. THORBURN A (2020) Crosstalk between autophagy and apoptosis: mechanisms and therapeutic implications [J]. Prog Mol Biol Transl Sci 172:55–65

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (grant number: 31801191), Research Fund of Lanzhou University (grant number: lzukqky-2019-t01, 533000-0711000-98-132, 20JR10RA653-ZDKF20210103), the Key Research Fund of Gansu Province (grant number: 21YF5GA100).

Author information

Authors and Affiliations

  1. School of Dentistry, Lanzhou University, No. 199 Donggang Xi Lu, Lanzhou, Gansu Province, 730000, P. R. China

    Yiheng Wang, Xinyi Li, Xiongtao Zhou, Tao Wang, Yuan Liu, Jianbao Feng & Xiangyi He

  2. Department of Preventive Veterinary Medicine, College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, R.P. China

    Zhidong Zhang & Yanmin Li

  3. Lanzhou Veterinary Research Institute, Chinese Academy of Agriculture Sciences, Lanzhou, 730000, Gansu, P. R. China

    Xiaodong Qin

  4. Key Laboratory of Functional Genomic and Molecular Diagnosis of Gansu Province, Lanzhou, 730030, P. R. China

    Xiangyi He

Authors
  1. Yiheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinyi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiongtao Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianbao Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaodong Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhidong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yanmin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiangyi He
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Xiangyi He and Zhidong Zhang contributed to the conception and design of this study. Yanmin Li and Xiaodong Qin contributed to experimental design. Yiheng Wang and Xinyi Li conceived the idea and wrote the manuscript. Yiheng Wang, Xiongtao Zhou, Yuan Liu, Tao Wang and Jianbao Feng performed the experiments, data acquisition and analysis. All the authors have given final approval of this article.

Corresponding authors

Correspondence to Yanmin Li or Xiangyi He.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Informed consent

Informed consent was obtained from the participant included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Li, X., Zhou, X. et al. Regulation of proliferation and apoptosis of aging periodontal ligament cells by autophagy-related gene 7. Mol Biol Rep 50, 6361–6372 (2023). https://doi.org/10.1007/s11033-023-08473-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-023-08473-7

Keywords

Search

Navigation