Effect of naringenin on osteogenic differentiation of human periodontal ligament stem cells

doi:10.12307/2022.143

Abstract

Abstract: BACKGROUND: Naringenin has various physiological activities such as anti-bacterial, anti-inflammatory, anti-fibrosis, and anti-oxidation, and is widely used in the fields of medicine and food. Recent studies have shown that naringenin can effectively promote the osteogenic differentiation of mesenchymal stem cells, but it is unclear whether naringenin regulates the osteogenic differentiation of periodontal ligament stem cells.
OBJECTIVE: To investigate the effects of naringenin with different concentrations on the osteogenic differentiation of human periodontal ligament stem cells.
METHODS: The primary human periodontal ligament stem cells were isolated and cultured. After treatment with naringenin at concentrations of 10, 100 nmol/L, 1, 10, 100 μmol/L and 1 mmol/L for 72 hours, the cytotoxicity of naringenin on periodontal ligament stem cells was measured via CCK-8 assays. The third generation of human periodontal ligament stem cells was cultured with osteogenic medium containing 0, 1, 10 and 100 μmol/L naringenin respectively. Alkaline phosphatase staining and activity detection were performed after 3, 5, and 7 days. Real-time PCR was used to detect the expression of osteogenic factors including Runx2, osteopontin and osteocalcin in human periodontal ligament stem cells after induction for 7 days. Alizarin red staining and quantitative determination of mineralized nodule were performed after induction for 14 days.
RESULTS AND CONCLUSION: Naringenin at a concentration of 10 nmol/L-100 μmol/L has no cytotoxicity to human periodontal ligament stem cells, and naringenin at a concentration of 1 mmol/L has obvious cytandotoxicity to human periodontal ligament stem cells. An appropriate concentration of naringenin (1-100 μmol/L) significantly promotes the increase of alkaline phosphatase activity and mineral deposition and upregulates the gene expression of Runx2, osteopontin and osteocalcin. The results showed that naringenin can significantly promote the osteogenic differentiation of human periodontal ligament stem cells, and the ability to promote osteogenic differentiation is strongest at 100 μmol/L.

Key words: stem cells, human periodontal ligament stem cells, naringenin, cytotoxicity, osteoggenesis, differentiation, factor

CLC Number:

Luo Xiaoling, Zhang Li, Yang Maohua, Xu Jie, Xu Xiaomei. Effect of naringenin on osteogenic differentiation of human periodontal ligament stem cells[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(7): 1051-1056.

Figures/Tables 8

References

[1] 孟焕新.牙周病学[M].北京:人民卫生出版社,2012:168-171.
[2] QIU W, WU BL, FANG FC. Overview of noncoding RNAs involved in the osteogenic differentiation of periodontal ligament stem cells. World J Stem Cells. 2020;12(4):251-265.
[3] JIN YZ, LEE JH. Mesenchymal Stem Cell Therapy for Bone Regeneration. Clin Orthop Surg. 2018;10(3):271-278.
[4] LUI PP, WONG OT, LEE YW. Transplantation of tendon-derived stem cells pre-treated with connective tissue growth factor and ascorbic acid in vitro promoted better tendon repair in a patellar tendon window injury rat model. Cytotherapy. 2016;18(1):99-112.
[5] KOVATS S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell Immunol. 2015;294(2):63-69.
[6] DHALIWAL A, PELKA S, GRAY DS, et al. Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules. Sci Rep. 2018; 8(1):16289.
[7] YANG Y, CHIN A, ZHANG L, et al. The role of traditional Chinese medicines in osteogenesis and angiogenesis. Phytother Res. 2014; 28(1):1-8.
[8] 张骞予,杨鸫祥,楼家晖.补肾中药诱导骨髓间充质干细胞增殖分化防治骨质疏松的究进展[J].中华中医药学刊,2020,38(3):193-195.
[9] CHEN R, QI QL, WANG MT, et al. Therapeutic potential of naringin: an overview. Pharm Biol. 2016;54(12):3203-3210.
[10] 唐镜,谭若兰,吕中建,等.柚皮素的提取及其抗癌作用研究进展[J].绿色科技,2019(8):240-244.
[11] ZENG W, JIN L, ZHANG F, et al. Naringenin as a potential immunomodulator in therapeutics. Pharmacol Res. 2018;135:122-126.
[12] SWARNKAR G, SHARAN K, SIDDIQUI JA, et al. A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts. Br J Pharmacol. 2012;165(5):1526-1542.
[13] MING LG, GE BF, WANG MG, et al. Comparison between 8-prenylnarigenin and narigenin concerning their activities on promotion of rat bone marrow stromal cells’ osteogenic differentiation in vitro. Cell Prolif. 2012;45(6):508-515.
[14] 张同凯.柚皮素对牙龈成纤维细胞的增殖和成骨分化的影响[J].医学临床研究,2019,36(3):527-529.
[15] HERNÁNDEZ-MONJARAZ B, SANTIAGO-OSORIO E, MONROY-GARCÍA A, et al. Mesenchymal Stem Cells of Dental Origin for Inducing Tissue Regeneration in Periodontitis: A Mini-Review. Int J Mol Sci. 2018;19(4): 944.
[16] TRUBIANI O, PIZZICANNELLA J, CAPUTI S, et al. Periodontal Ligament Stem Cells: Current Knowledge and Future Perspectives. Stem Cells Dev. 2019;28(15):995-1003.
[17] YU GY, ZHENG GZ, CHANG B, et al. Naringin Stimulates Osteogenic Differentiation of Rat Bone Marrow Stromal Cells via Activation of the Notch Signaling Pathway. Stem Cells Int. 2016;2016:7130653.
[18] ALAM MA, SUBHAN N, RAHMAN MM, et al. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr. 2014;5(4):404-417.
[19] YUE J, YANG H, LIU S, et al. Influence of naringenin on the biofilm formation of Streptococcus mutans. J Dent. 2018;76:24-31.
[20] WANG W, WU C, TIAN B, et al. The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis. Int J Mol Sci. 2014;15(12):21913-21934.
[21] YU Z, GAUTHIER P, TRAN QT, et al. Differential Properties of Human ALP+ Periodontal Ligament Stem Cells vs Their ALP- Counterparts. J Stem Cell Res Ther. 2015;5(7):292.
[22] KAWANE T, QIN X, JIANG Q, et al. Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3. Sci Rep. 2018;8(1):13551.
[23] KUSUYAMA J, AMIR MS, ALBERTSON BG, et al. JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4). FASEB J. 2019;33(6):7331-7347.
[24] ARIFFIN SH, MANOGARAN T, ABIDIN IZ, et al. A Perspective on Stem Cells as Biological Systems that Produce Differentiated Osteoblasts and Odontoblasts. Curr Stem Cell Res Ther. 2017;12(3):247-259.