Gingival Fibroblasts Are Sensitive to Oral Cell Lysates Indicated by Their IL11 Expression
Abstract
:1. Introduction
2. Methods
2.1. Cell Lines and Primary Cells
2.2. Cell Lysates and Basic Experimental Setting
2.3. RNA Sequencing
2.4. Reverse Transcription Quantitative Real-Time PCR (RT-qPCR)
2.5. Immunoassay
2.6. Immunofluorescent Analysis
2.7. Statistical Analysis
3. Results
3.1. Gene Expression Screening Assay
3.2. IL11 Expression Analysis
3.3. IL11 Immunoassay
3.4. Smad2/3 Nuclear Translocation
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Nanci, A.; Bosshardt, D.D. Structure of periodontal tissues in health and disease. Periodontol. 2000 2006, 40, 11–28. [Google Scholar] [CrossRef] [PubMed]
- Sculean, A.; Gruber, R.; Bosshardt, D.D. Soft tissue wound healing around teeth and dental implants. J. Clin. Periodontol. 2014, 41, S6–S22. [Google Scholar] [CrossRef] [PubMed]
- Aghvami, M.; Brunski, J.B.; Serdar Tulu, U.; Chen, C.H.; Helms, J.A. A Thermal and Biological Analysis of Bone Drilling. J. Biomech. Eng. 2018, 140, 1010101–1010108. [Google Scholar] [CrossRef]
- Andreev, D.; Liu, M.; Weidner, D.; Kachler, K.; Faas, M.; Gruneboom, A.; Schlotzer-Schrehardt, U.; Munoz, L.E.; Steffen, U.; Grotsch, B.; et al. Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin. J. Clin. Investig. 2020, 130, 4811–4830. [Google Scholar] [CrossRef] [PubMed]
- McHugh, J. Osteocyte death promotes bone loss. Nat. Rev. Rheumatol. 2020, 16, 539. [Google Scholar] [CrossRef] [PubMed]
- Cobb, C.M. Clinical significance of non-surgical periodontal therapy: An evidence-based perspective of scaling and root planing. J. Clin. Periodontol. 2002, 29, 6–16. [Google Scholar] [CrossRef]
- Williams, V.D. Electrosurgery and wound healing: A review of the literature. J. Am. Dent. Assoc. 1984, 108, 220–222. [Google Scholar] [CrossRef]
- Kujan, O.; Azzeghaiby, S.N.; Tarakji, B.; Abuderman, A.; Sakka, S. Cryosurgery of the oral and peri-oral region: A literature review of the mechanism, tissue response, and clinical applications. J. Investig. Clin. Dent. 2013, 4, 71–77. [Google Scholar] [CrossRef]
- Kumar, N.; Maher, N.; Amin, F.; Ghabbani, H.; Zafar, M.S.; Rodriguez-Lozano, F.J.; Onate-Sanchez, R.E. Biomimetic Approaches in Clinical Endodontics. Biomimetics 2022, 7, 229. [Google Scholar] [CrossRef]
- Lopez-Garcia, S.; Pecci-Lloret, M.P.; Garcia-Bernal, D.; Guerrero-Girones, J.; Pecci-Lloret, M.R.; Rodriguez-Lozano, F.J. Are Denture Adhesives Safe for Oral Cells? J. Prosthodont. 2021, 30, 65–70. [Google Scholar] [CrossRef]
- D’Arcy, M.S. Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol. Int. 2019, 43, 582–592. [Google Scholar] [CrossRef]
- Lucas, H.; Bartold, P.M.; Dharmapatni, A.A.; Holding, C.A.; Haynes, D.R. Inhibition of apoptosis in periodontitis. J. Dent. Res. 2010, 89, 29–33. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Ke, X.; Yan, F.; Lei, L.; Li, H. Necroptosis in the periodontal homeostasis: Signals emanating from dying cells. Oral Dis. 2018, 24, 900–907. [Google Scholar] [CrossRef] [PubMed]
- Sordi, M.B.; Magini, R.S.; Panahipour, L.; Gruber, R. Pyroptosis-Mediated Periodontal Disease. Int. J. Mol. Sci. 2021, 23, 372. [Google Scholar] [CrossRef] [PubMed]
- Nikoloudaki, G.; Creber, K.; Hamilton, D.W. Wound healing and fibrosis: A contrasting role for periostin in skin and the oral mucosa. Am. J. Physiol. Cell Physiol. 2020, 318, C1065–C1077. [Google Scholar] [CrossRef] [PubMed]
- Kiuchi, M.; Yamamura, T.; Okudera, M.; Souksavanh, V.; Ishigami, T.; Iwase, T.; Warnakulasuriya, S.; Komiyama, K. An assessment of mast cells and myofibroblasts in denture-induced fibrous hyperplasia. J. Oral. Pathol. Med. 2014, 43, 53–60. [Google Scholar] [CrossRef]
- De Oliveira Mussel, R.L.; Costa, A.M.; Mandarim-de-Lacerda, C.A. Implants of an adhesive resin, a calcium hydroxide, and a glass-ionomer cement cause reactional fibrosis with mast cells involvement in rats. Quintessence Int. 2007, 38, e348–e354. [Google Scholar]
- Cook, S.A. The Pathobiology of Interleukin 11 in Mammalian Disease is Likely Explained by its Essential Evolutionary Role for Fin Regeneration. J. Cardiovasc. Transl. Res. 2023, 16, 755–757. [Google Scholar] [CrossRef]
- Widjaja, A.A.; Viswanathan, S.; Shekeran, S.G.; Adami, E.; Lim, W.W.; Chothani, S.; Tan, J.; Goh, J.W.T.; Chen, H.M.; Lim, S.Y.; et al. Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease. Nat. Commun. 2022, 13, 7497. [Google Scholar] [CrossRef]
- Schafer, S.; Viswanathan, S.; Widjaja, A.A.; Lim, W.W.; Moreno-Moral, A.; DeLaughter, D.M.; Ng, B.; Patone, G.; Chow, K.; Khin, E.; et al. IL-11 is a crucial determinant of cardiovascular fibrosis. Nature 2017, 552, 110–115. [Google Scholar] [CrossRef]
- Ng, B.; Dong, J.; D’Agostino, G.; Viswanathan, S.; Widjaja, A.A.; Lim, W.W.; Ko, N.S.J.; Tan, J.; Chothani, S.P.; Huang, B.; et al. Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Sci. Transl. Med. 2019, 11, eaaw1237. [Google Scholar] [CrossRef] [PubMed]
- Adami, E.; Viswanathan, S.; Widjaja, A.A.; Ng, B.; Chothani, S.; Zhihao, N.; Tan, J.; Lio, P.M.; George, B.L.; Altunoglu, U.; et al. IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGFbeta-mediated activation of dermal fibroblasts. Rheumatology 2021, 60, 5820–5826. [Google Scholar] [CrossRef] [PubMed]
- Widjaja, A.A.; Singh, B.K.; Adami, E.; Viswanathan, S.; Dong, J.; D’Agostino, G.A.; Ng, B.; Lim, W.W.; Tan, J.; Paleja, B.S.; et al. Inhibiting Interleukin 11 Signaling Reduces Hepatocyte Death and Liver Fibrosis, Inflammation, and Steatosis in Mouse Models of Nonalcoholic Steatohepatitis. Gastroenterology 2019, 157, 777–792.e14. [Google Scholar] [CrossRef]
- Dong, B.; Hiasa, M.; Higa, Y.; Ohnishi, Y.; Endo, I.; Kondo, T.; Takashi, Y.; Tsoumpra, M.; Kainuma, R.; Sawatsubashi, S.; et al. Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis. Nat. Commun. 2022, 13, 7194. [Google Scholar] [CrossRef] [PubMed]
- Yucel, O.O.; Berker, E.; Gariboglu, S.; Otlu, H. Interleukin-11, interleukin-1beta, interleukin-12 and the pathogenesis of inflammatory periodontal diseases. J. Clin. Periodontol. 2008, 35, 365–370. [Google Scholar] [CrossRef]
- Sonis, S.T.; Peterson, R.L.; Edwards, L.J.; Lucey, C.A.; Wang, L.; Mason, L.; Login, G.; Ymamkawa, M.; Moses, G.; Bouchard, P.; et al. Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral Oncol. 2000, 36, 373–381. [Google Scholar] [CrossRef]
- Schierano, G.; Bassi, F.; Gassino, G.; Mareschi, K.; Bellone, G.; Preti, G. Cytokine production and bone remodeling in patients wearing overdentures on oral implants. J. Dent. Res. 2000, 79, 1675–1682. [Google Scholar] [CrossRef]
- Strauss, F.J.; Stahli, A.; Beer, L.; Mitulovic, G.; Gilmozzi, V.; Haspel, N.; Schwab, G.; Gruber, R. Acid bone lysate activates TGFbeta signalling in human oral fibroblasts. Sci. Rep. 2018, 8, 16065. [Google Scholar] [CrossRef]
- Panahipour, L.; Omerbasic, A.; Nasirzade, J.; Gruber, R. TGF-beta Activity of a Demineralized Bone Matrix. Int. J. Mol. Sci. 2021, 22, 664. [Google Scholar] [CrossRef]
- Peng, J.; Nemec, M.; Brolese, E.; Bosshardt, D.D.; Schaller, B.; Buser, D.; Gruber, R. Bone-Conditioned Medium Inhibits Osteogenic and Adipogenic Differentiation of Mesenchymal Cells In Vitro. Clin. Implant. Dent. Relat. Res. 2015, 17, 938–949. [Google Scholar] [CrossRef]
- Nasirzade, J.; Kargarpour, Z.; Mitulovic, G.; Strauss, F.J.; Panahipour, L.; Schwarz, F.; Gruber, R. Proteomic and genomic analysis of acid dentin lysate with focus on TGF-beta signaling. Sci. Rep. 2021, 11, 12247. [Google Scholar] [CrossRef]
- Kargarpour, Z.; Nasirzade, J.; Panahipour, L.; Miron, R.J.; Gruber, R. Liquid Platelet-Rich Fibrin and Heat-Coagulated Albumin Gel: Bioassays for TGF-beta Activity. Materials 2020, 13, 3466. [Google Scholar] [CrossRef]
- Stahli, A.; Bosshardt, D.; Sculean, A.; Gruber, R. Emdogain-regulated gene expression in palatal fibroblasts requires TGF-betaRI kinase signaling. PLoS ONE 2014, 9, e105672. [Google Scholar] [CrossRef] [PubMed]
- Panahipour, L.; Husejnovic, S.; Nasirzade, J.; Semelmayer, S.; Gruber, R. Micellar Casein and Whey Powder Hold a TGF-beta Activity and Regulate ID Genes In Vitro. Molecules 2021, 26, 507. [Google Scholar] [CrossRef] [PubMed]
- Panahipour, L.; Stahli, A.; Haiden, N.; Gruber, R. TGF-beta activity in cow milk and fermented milk products: An in vitro bioassay with oral fibroblasts. Arch. Oral. Biol. 2018, 95, 15–21. [Google Scholar] [CrossRef]
- Lim, W.W.; Ng, B.; Widjaja, A.; Xie, C.; Su, L.; Ko, N.; Lim, S.Y.; Kwek, X.Y.; Lim, S.; Cook, S.A.; et al. Transgenic interleukin 11 expression causes cross-tissue fibro-inflammation and an inflammatory bowel phenotype in mice. PLoS ONE 2020, 15, e0227505. [Google Scholar] [CrossRef]
- Ng, B.; Dong, J.; Viswanathan, S.; Widjaja, A.A.; Paleja, B.S.; Adami, E.; Ko, N.S.J.; Wang, M.; Lim, S.; Tan, J.; et al. Fibroblast-specific IL11 signaling drives chronic inflammation in murine fibrotic lung disease. FASEB J. 2020, 34, 11802–11815. [Google Scholar] [CrossRef] [PubMed]
- Gregg, R.K.; Jain, R.; Schoenleber, S.J.; Divekar, R.; Bell, J.J.; Lee, H.H.; Yu, P.; Zaghouani, H. A sudden decline in active membrane-bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes. J. Immunol. 2004, 173, 7308–7316. [Google Scholar] [CrossRef]
- Ahn, Y.O.; Lee, J.C.; Sung, M.W.; Heo, D.S. Presence of membrane-bound TGF-beta1 and its regulation by IL-2-activated immune cell-derived IFN-gamma in head and neck squamous cell carcinoma cell lines. J. Immunol. 2009, 182, 6114–6120. [Google Scholar] [CrossRef]
- Yang, W.; Zhang, S.; Li, T.; Zhou, Z.; Pan, J. Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-beta/Smad pathway. Acta Biochim. Biophys. Sin. 2022, 55, 262–273. [Google Scholar] [CrossRef]
- Carroll, M.; Alliston, T.; Dole, N. The Multifaceted Effects of Osteocytic TGFbeta Signaling on the Skeletal and Extraskeletal Functions of Bone. Curr. Osteoporos. Rep. 2023, 21, 414–425. [Google Scholar] [CrossRef] [PubMed]
- Stack, M.E.; Mishra, S.; Parimala Chelvi Ratnamani, M.; Wang, H.; Gold, L.I.; Wang, H. Biomimetic Extracellular Matrix Nanofibers Electrospun with Calreticulin Promote Synergistic Activity for Tissue Regeneration. ACS Appl. Mater. Interfaces 2022, 14, 51683–51696. [Google Scholar] [CrossRef] [PubMed]
- Baberg, F.; Geyh, S.; Waldera-Lupa, D.; Stefanski, A.; Zilkens, C.; Haas, R.; Schroeder, T.; Stuhler, K. Secretome analysis of human bone marrow derived mesenchymal stromal cells. Biochim. Biophys. Acta Proteins Proteom. 2019, 1867, 434–441. [Google Scholar] [CrossRef] [PubMed]
- Noh, S.M.; Abdul Kadir, S.H.; Crowston, J.G.; Subrayan, V.; Vasudevan, S. Effects of ranibizumab on TGF-beta1 and TGF-beta2 production by human Tenon’s fibroblasts: An in vitro study. Mol. Vis. 2015, 21, 1191–1200. [Google Scholar] [PubMed]
- Nevers, T.; Salvador, A.M.; Velazquez, F.; Ngwenyama, N.; Carrillo-Salinas, F.J.; Aronovitz, M.; Blanton, R.M.; Alcaide, P. Th1 effector T cells selectively orchestrate cardiac fibrosis in nonischemic heart failure. J. Exp. Med. 2017, 214, 3311–3329. [Google Scholar] [CrossRef]
- Yang, J.J.; Wang, D.D.; Sun, T.Y. Flagellin of Pseudomonas aeruginosa induces transforming growth factor beta 1 expression in normal bronchial epithelial cells through mitogen activated protein kinase cascades. Chin. Med. J. 2011, 124, 599–605. [Google Scholar]
- Byeon, Y.E.; Ryu, H.H.; Park, S.S.; Koyama, Y.; Kikuchi, M.; Kim, W.H.; Kang, K.S.; Kweon, O.K. Paracrine effect of canine allogenic umbilical cord blood-derived mesenchymal stromal cells mixed with beta-tricalcium phosphate on bone regeneration in ectopic implantations. Cytotherapy 2010, 12, 626–636. [Google Scholar] [CrossRef]
- Sasaki, A.; Naganuma, H.; Satoh, E.; Kawataki, T.; Amagasaki, K.; Nukui, H. Participation of thrombospondin-1 in the activation of latent transforming growth factor-beta in malignant glioma cells. Neurol. Med. Chir. 2001, 41, 253–258; discussion 258–259. [Google Scholar] [CrossRef]
- Effenberger, M.; Widjaja, A.A.; Grabherr, F.; Schaefer, B.; Grander, C.; Mayr, L.; Schwaerzler, J.; Enrich, B.; Moser, P.; Fink, J.; et al. Interleukin-11 drives human and mouse alcohol-related liver disease. Gut 2023, 72, 168–179. [Google Scholar] [CrossRef] [PubMed]
- Ng, B.; Xie, C.; Su, L.; Kuthubudeen, F.F.; Kwek, X.Y.; Yeong, D.; Pua, C.J.; Cook, S.A.; Lim, W.W. IL11 (Interleukin-11) Causes Emphysematous Lung Disease in a Mouse Model of Marfan Syndrome. Arter. Thromb. Vasc. Biol. 2023, 43, 739–754. [Google Scholar] [CrossRef] [PubMed]
- Ng, B.; Widjaja, A.A.; Viswanathan, S.; Dong, J.; Chothani, S.P.; Lim, S.; Shekeran, S.G.; Tan, J.; McGregor, N.E.; Walker, E.C.; et al. Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis. Sci. Rep. 2021, 11, 14088. [Google Scholar] [CrossRef] [PubMed]
- Dobaczewski, M.; Bujak, M.; Li, N.; Gonzalez-Quesada, C.; Mendoza, L.H.; Wang, X.F.; Frangogiannis, N.G. Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ. Res. 2010, 107, 418–428. [Google Scholar] [CrossRef] [PubMed]
- Kargarpour, Z.; Panahipour, L.; Miron, R.J.; Gruber, R. Blood Clots versus PRF: Activating TGF-beta Signaling and Inhibiting Inflammation In Vitro. Int. J. Mol. Sci. 2022, 23, 5897. [Google Scholar] [CrossRef] [PubMed]
- Di Summa, F.; Kargarpour, Z.; Nasirzade, J.; Stahli, A.; Mitulovic, G.; Panic-Jankovic, T.; Koller, V.; Kaltenbach, C.; Muller, H.; Panahipour, L.; et al. TGFbeta activity released from platelet-rich fibrin adsorbs to titanium surface and collagen membranes. Sci. Rep. 2020, 10, 10203. [Google Scholar] [CrossRef]
- Becerik, S.; Ozturk, V.O.; Atmaca, H.; Atilla, G.; Emingil, G. Gingival crevicular fluid and plasma acute-phase cytokine levels in different periodontal diseases. J. Periodontol. 2012, 83, 1304–1313. [Google Scholar] [CrossRef]
- Taylor, R.C.; Cullen, S.P.; Martin, S.J. Apoptosis: Controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 2008, 9, 231–241. [Google Scholar] [CrossRef]
- Rodriguez-Lozano, F.J.; Garcia-Bernal, D.; Aznar-Cervantes, S.; Ros-Roca, M.A.; Alguero, M.C.; Atucha, N.M.; Lozano-Garcia, A.A.; Moraleda, J.M.; Cenis, J.L. Effects of composite films of silk fibroin and graphene oxide on the proliferation, cell viability and mesenchymal phenotype of periodontal ligament stem cells. J. Mater. Sci. Mater. Med. 2014, 25, 2731–2741. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Panahipour, L.; Abbasabadi, A.O.; Gruber, R. Gingival Fibroblasts Are Sensitive to Oral Cell Lysates Indicated by Their IL11 Expression. Bioengineering 2023, 10, 1193. https://doi.org/10.3390/bioengineering10101193
Panahipour L, Abbasabadi AO, Gruber R. Gingival Fibroblasts Are Sensitive to Oral Cell Lysates Indicated by Their IL11 Expression. Bioengineering. 2023; 10(10):1193. https://doi.org/10.3390/bioengineering10101193
Chicago/Turabian StylePanahipour, Layla, Azarakhsh Oladzad Abbasabadi, and Reinhard Gruber. 2023. "Gingival Fibroblasts Are Sensitive to Oral Cell Lysates Indicated by Their IL11 Expression" Bioengineering 10, no. 10: 1193. https://doi.org/10.3390/bioengineering10101193