Aspirin promotes osteogenic differentiation of human dental pulp stem cells

Yuan,Mengtong; Zhan,Yuanbo; Hu,Weiping; Li,Ying; Xie,Xiaohua; Miao,Nan; Jin,Han; Zhang,Bin

doi:10.3892/ijmm.2018.3801

Aspirin promotes osteogenic differentiation of human dental pulp stem cells

Authors:
- Mengtong Yuan
- Yuanbo Zhan
- Weiping Hu
- Ying Li
- Xiaohua Xie
- Nan Miao
- Han Jin
- Bin Zhang
View Affiliations

Affiliations: Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: August 2, 2018 https://doi.org/10.3892/ijmm.2018.3801
Pages: 1967-1976
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Human dental pulp stem cells (hDPSCs) possess self‑renewal and osteogenic differentiation properties, and have been used for orofacial bone regeneration and periodontal treatment. Aspirin has been demonstrated to enhance the regeneration of bone marrow mesenchymal stem cells (MSCs); however, the impact of aspirin on the osteogenic differentiation of hDPSCs remains unknown. In the present study, hDPSCs were characterized by flow cytometry, while their clonogenic potential and multipotency were assessed using alizarin red, Oil red O and alcian blue staining. The effect of aspirin on hDPSC viability was assessed using Cell Counting Kit‑8 assay. Osteogenic capacity was examined by alkaline phosphatase activity, alizarin red staining, reverse transcription‑polymerase chain reaction and western blotting. Furthermore, in vivo cranial defects were established in Sprague‑Dawley rats to evaluate the effect of aspirin on hDPSC‑based bone regeneration. Anorganic bovine bone was used as a bone replacement material and as the carrier for hDPSCs. New bone formation was observed through radiographic and histological analysis. The study demonstrated that hDPSCs expressed MSC markers and possessed multipotency in vitro. Aspirin was non‑toxic to hDPSCs at a concentration of ≤100 µg/ml and enhanced the osteogenesis of hDPSCs in vitro. Aspirin significantly increased hDPSC‑based bone formation in the rat cranial defect model at 8 or 12 weeks post‑implantation (P<0.05). The data suggested that aspirin promotes the osteogenic potential of hDPSCs in vitro and in vivo. Overall, the present study indicated that aspirin improves the bone regeneration capacity of hDPSCs.

View Figures

View References

1	Gronthos S, Mankani M, Brahim J, Robey PG and Shi S: Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 97:13625–13630. 2000. View Article : Google Scholar : PubMed/NCBI
2	Wei X, Ling J, Wu L, Liu L and Xiao Y: Expression of mineralization markers in dental pulp cells. J Endod. 33:703–708. 2007. View Article : Google Scholar : PubMed/NCBI
3	Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG and Shi S: Stem cell properties of human dental pulp stem cells. J Dent Res. 81:531–535. 2002. View Article : Google Scholar : PubMed/NCBI
4	Liu H, Gronthos S and Shi S: Dental pulp stem cells. Methods Enzymol. 419:99–113. 2006. View Article : Google Scholar : PubMed/NCBI
5	About I, Bottero MJ, de Denato P, Camps J, Franquin JC and Mitsiadis TA: Human dentin production in vitro. Exp Cell Res. 258:33–41. 2000. View Article : Google Scholar : PubMed/NCBI
6	Zhao Y, Wang L, Jin Y and Shi S: Fas ligand regulates the immu-nomodulatory properties of dental pulp stem cells. J Dent Res. 91:948–954. 2012. View Article : Google Scholar : PubMed/NCBI
7	Smith JB and Willis AL: Aspirin selectively inhibits pros-taglandin production in human platelets. Nat New Biol. 231:235–237. 1971. View Article : Google Scholar : PubMed/NCBI
8	Yamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, Patel V, Gutkind S, Young M, Gronthos S, et al: Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS One. 3:e26152008. View Article : Google Scholar : PubMed/NCBI
9	Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C, Xu X, Yang R, Chen W, Wang S and Shi S: Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nat Med. 17. pp. 1594–1601. 2011, View Article : Google Scholar
10	Cao Y, Xiong J, Mei S, Wang F, Zhao Z, Wang S and Liu Y: Aspirin promotes bone marrow mesenchymal stem cell-based calvarial bone regeneration in mini swine. Stem Cell Res Ther. 6:2102015. View Article : Google Scholar : PubMed/NCBI
11	Liu Y, Chen C, Liu S, Liu D, Xu X, Chen X and Shi S: Acetylsalicylic acid treatment improves differentiation and immunomodulation of SHED. J Dent Res. 94:209–218. 2015. View Article : Google Scholar :
12	Abd Rahman F, Mohd Ali J, Abdullah M, Abu Kasim NH and Musa S: Aspirin enhances osteogenic potential of periodontal ligament stem cells (PDLSCs) and modulates the expression profile of growth factor-associated genes in PDLSCs. J Periodontol. 87:837–847. 2016. View Article : Google Scholar : PubMed/NCBI
13	Liu H, Li W, Liu Y, Zhang X and Zhou Y: Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin. Stem Cell Res Ther. 6:2002015. View Article : Google Scholar : PubMed/NCBI
14	Bauer DC, Orwoll ES, Fox KM, Vogt TM, Lane NE, Hochberg MC, Stone K and Nevitt MC: Aspirin and NSAID use in older women: Effect on bone mineral density and fracture risk. J Bone Miner Res. 11:29–35. 1996. View Article : Google Scholar : PubMed/NCBI
15	Kuznetsov SA, Krebsbach PH, Satomura K, Kerr J, Riminucci M, Benayahu D and Robey PG: Single-colony derived strains of human marrow stromal fibroblasts form bone after transplantation in vivo. J Bone Miner Res. 12:1335–1347. 1997. View Article : Google Scholar : PubMed/NCBI
16	Lei M, Li K, Li B, Gao LN, Chen FM and Jin Y: Mesenchymal stem cell characteristics of dental pulp and periodontal ligament stem cells after in vivo transplantation. Biomaterials. 35:6332–6343. 2014. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔ^C T method. Methods. 25:402–408. 2001. View Article : Google Scholar
18	Spicer PP, Kretlow JD, Young S, Jansen JA, Kasper FK and Mikos AG: Evaluation of bone regeneration using the rat critical size calvarial defect. Nat Protoc. 7:1918–1929. 2012. View Article : Google Scholar : PubMed/NCBI
19	Shi S, Gronthos S, Chen S, Reddi A, Counter CM, Robey PG and Wang CY: Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol. 20:587–591. 2002. View Article : Google Scholar : PubMed/NCBI
20	Nuti N, Corallo C, Chan BM, Ferrari M and Gerami-Naini B: Multipotent differentiation of human dental pulp stem cells: A literature review. Stem Cell Rev. 12:511–523. 2016. View Article : Google Scholar : PubMed/NCBI
21	Liu M, Sun Y, Liu Y, Yuan M, Zhang Z and Hu W: Modulation of the differentiation of dental pulp stem cells by different concentrations of β-glycerophosphate. Molecules. 17:1219–1232. 2012. View Article : Google Scholar : PubMed/NCBI
22	Wang Y, Yao J, Yuan M, Zhang Z and Hu W: Osteoblasts can induce dental pulp stem cells to undergo osteogenic differentiation. Cytotechnology. 65:223–231. 2013. View Article : Google Scholar :
23	Ferro F, Spelat R, Beltrami AP, Cesselli D and Curcio F: Isolation and characterization of human dental pulp derived stem cells by using media containing low human serum percentage as clinical grade substitutes for bovine serum. PLoS One. 7:e489452012. View Article : Google Scholar : PubMed/NCBI
24	Shi S and Gronthos S: Perivascular niche of postnatal mesen-chymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 18:696–704. 2003. View Article : Google Scholar : PubMed/NCBI
25	Gronthos S and Zannettino AC: A method to isolate and purify human bone marrow stromal stem cells. Methods Mol Biol. 449:45–57. 2008.PubMed/NCBI
26	Yu J, He H, Tang C, Zhang G, Li Y, Wang R, Shi J and Jin Y: Differentiation potential of STRO-1⁺ dental pulp stem cells changes during cell passaging. BMC Cell Biol. 11:322010. View Article : Google Scholar
27	Tang J, Xiong J, Wu T, Tang Z, Ding G, Zhang C, Wang S and Liu Y: Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ₂/PPARγ/TGF-β1 pathway. Stem Cells Dev. 23:2093–2103. 2014. View Article : Google Scholar : PubMed/NCBI
28	Sun L, Blair HC, Peng Y, Zaidi N, Adebanjo OA, Wu XB, Wu XY, Iqbal J, Epstein S, Abe E, et al: Calcineurin regulates bone formation by the osteoblast. Proc Natl Acad Sci USA. 102:17130–17135. 2005. View Article : Google Scholar : PubMed/NCBI
29	Wiesmann HP, Meyer U, Plate U and Höhling HJ: Aspects of collagen mineralization in hard tissue formation. Int Rev Cytol. 242:121–156. 2005. View Article : Google Scholar
30	Graziano A, D'Aquino R, Laino G and Papaccio G: Dental pulp stem cells: A promising tool for bone regeneration. Stem Cell Rev. 4:21–26. 2008. View Article : Google Scholar : PubMed/NCBI
31	Morad G, Kheiri L and Khojasteh A: Dental pulp stem cells for in vivo bone regeneration: A systematic review of literature. Arch Oral Biol. 58:1818–1827. 2013. View Article : Google Scholar : PubMed/NCBI
32	Sculean A, Chiantella GC, Windisch P, Gera I and Reich E: Clinical evaluation of an enamel matrix protein derivative (Emdogain) combined with a bovine-derived xenograft (Bio-Oss) for the treatment of intrabony periodontal defects in humans. Int J Periodontics Restorative Dent. 22:259–267. 2002.PubMed/NCBI
33	Valentini P and Abensur DJ: Maxillary sinus grafting with anorganic bovine bone: A clinical report of long-term results. Int J Oral Maxillofac Implants. 18:556–560. 2003.PubMed/NCBI
34	Klinge B, Alberius P, Isaksson S and Jönsson J: Osseous reponse to implant natural bone mineral and synthetic hydroxylapatite ceramic in the repair of experimental skull bone defects. J Oral Maxillofac Surg. 50:241–249. 1992. View Article : Google Scholar : PubMed/NCBI
35	Jensen SS, Aaboe M, Pinholt EM, Hjørting-Hansen E, Melsen F and Ruyter IE: Tissue reaction and material characteristics of four bone substitutes. Int J Oral Maxillofac Implants. 11:55–66. 1996.PubMed/NCBI
36	Berglundh T and Lindhe J: Healing around implants placed in bone defects treated with Bio-Oss. An experimental study in the dog. Clin Oral Implants Res. 8:117–124. 1997. View Article : Google Scholar : PubMed/NCBI
37	Piattelli M, Favero GA, Scarano A, Orsini G and Piattelli A: Bone reactions to anorganic bovine bone (Bio-Oss) used in sinus augmentation procedures: A histologic long-term report of 20 cases in humans. Int J Oral Maxillofac Implants. 14:835–840. 1999.PubMed/NCBI
38	Cowan CM, Shi YY, Aalami OO, Chou YF, Mari C, Thomas R, Quarto N, Contag CH, Wu B and Longaker MT: Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol. 22:560–567. 2004. View Article : Google Scholar : PubMed/NCBI