Effects of naringin on healing of tooth extraction wound in osteoporotic rats

doi:10.12307/2023.592

Abstract

Abstract: BACKGROUND: Naringin, a monomer compound of Traditional Chinese medicine, has anti-inflammatory and osteogenic effects, but its effect on the healing rate of tooth extraction wounds is not clear.
OBJECTIVE: To investigate the effect of naringin on the healing rate of tooth extraction wounds in rat models of osteoporosis.
METHODS: Forty-eight female Sprague-Dawley rats were randomly divided into sham-operation group (n=14) and ovariectomized group (n=34). In the ovariectomized group, bilateral ovaries were removed to establish osteoporosis models. After 6 weeks, four rats in each group were randomly selected for MicroCT detection to confirm the modeling results. After successful modeling, the remaining rats were subject to tooth extraction and randomly divided into tooth extraction group (the remaining rats in the sham-operation group), control group, naringin group, and estradiol group, and the second molar of left maxillary was extracted. Naringin group was given naringin 300 mg/kg/d by gavage, estradiol group was given 17-β estradiol 20 μg/kg/d by subcutaneous injection, and tooth extraction group and control group were treated with the same volume of normal saline. After 4 weeks of intervention, the rat maxilla was separated for hematoxylin-eosin staining, Masson staining, and MicroCT detection. The expressions of osteoprotegerin and receptor activator of nuclear factor-κB ligand (RANKL) at mRNA and protein levels in the bone tissue around the tooth extraction wounds were also detected.
RESULTS AND CONCLUSION: After 6 weeks of castration, the bone volume fraction of the ovariectomized group decreased, indicating that the modeling of osteoporosis was successful. Four weeks after tooth extraction, compared with the control group, the naringin group and estradiol group had smaller trabecular separation and less loss of alveolar bone height, indicating that naringin could promote bone healing of tooth extraction wounds. Compared with the control group, the expression level of osteoprotegerin and RANKL in bone tissues around tooth extraction was increased and decreased respectively in the naringin and estradiol groups, indicating that naringin could up-regulate osteoprotegerin expression and down-regulate RANKL expression.

Key words: osteoporosis, naringin, tooth extraction, bone healing, OPG, RANKL, RANK, rat

CLC Number:

Huang Haozhe, Zheng Min, Li Na, Sun Libo, Lan Yuyan, Liu Min. Effects of naringin on healing of tooth extraction wound in osteoporotic rats[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(32): 5144-5149.

Figures/Tables 5

References

[1] PAVONE V, TESTA G, GIARDINA SMC, et al. Pharmacological Therapy of Osteoporosis: A Systematic Current Review of Literature. Front Pharmacol. 2017;8:803.
[2] JOHNELL O, KANIS JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17(12):1726-1733.
[3] KOTH VS, SALUM FG, DE FIGUEIREDO MAZ, et al. Repercussions of osteoporosis on the maxillofacial complex: a critical overview. J Bone Miner Metab. 2021;39(2):117-125.
[4] ARIOKA M, ZHANG X, LI Z, et al. Osteoporotic Changes in the Periodontium Impair Alveolar Bone Healing. J Dent Res. 2019;98(4):450-458.
[5] CHEN CH, WANG L, SERDAR TULU U, et al. An osteopenic/osteoporotic phenotype delays alveolar bone repair. Bone. 2018;112:212-219.
[6] 杨红梅. 1987-2019年中国老年人牙周病流行趋势的系统评价及meta分析 [D].重庆:重庆医科大学,2019.
[7] 国家卫生健康委员会官网.国家卫生健康委发布首个中国骨质疏松症流行病学调查结果[J].人口文摘,2018(11):55-56.
[8] NICOLIELO LFP, VAN DESSEL J, JACOBS R, et al. Relationship between trabecular bone architecture and early dental implant failure in the posterior region of the mandible. Clin Oral Implants Res. 2020;31(2):153-161.
[9] DO TA, LE HS, SHEN YW, et al. Risk Factors related to Late Failure of Dental Implant-A Systematic Review of Recent Studies. Int J Environ Res Public Health. 2020;17(11):3931.
[10] 李微, 张博, 张雨薇,等.雌激素调节骨代谢作用的研究进展 [J].中国骨质疏松杂志,2017,23(2):262-266.
[11] WAJANAVISIT W, SUPPACHOKMONGKORN S, WORATANARAT P, et al. The Association of Bone Mineral Density and G2014A Polymorphism in the Estrogen Receptor Alpha Gene in Osteoporotic Hip Fracture in Thai Population. J Med Assoc Thai. 2015;98 Suppl 8:S82-87.
[12] LAVRADOR P, GASPAR VM, MANO JF. Bioinspired bone therapies using naringin: applications and advances. Drug Discov Today. 2018;23(6):1293-1304.
[13] SHAO Y, YOU D, LOU Y, et al. Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells. ACS Omega. 2019; 4(21): 19350-19357.
[14] 刘小坡,冯云波,曹国龙,等. 柚皮苷对老年大鼠骨质疏松性骨折愈合的影响[J].中国临床药理学杂志,2020,36(9):1117-1120.
[15] 王庚启,王黎明,谢林,等.柚皮苷对去势大鼠骨质疏松性骨折愈合的影响[J].上海中医药大学学报,2016,30(4):73-79.
[16] CHEN LL, LEI LH, DING PH, et al. Osteogenic effect of Drynariae rhizoma extracts and Naringin on MC3T3-E1 cells and an induced rat alveolar bone resorption model. Arch Oral Biol. 2011;56(12):1655-1662.
[17] YASUDA H. Discovery of the RANKL/RANK/OPG system. J Bone Miner Metab. 2021;39(1):2-11.
[18] ZENG H, ZHAO X, WANG L, et al. Effects of Drynaria Total Flavonoid on the Microstructure of the Mandible in Ovariectomized Rats. Med Sci Monit. 2020;26: e926171.
[19] YU KE, ALDER KD, MORRIS MT, et al. Re-appraising the potential of naringin for natural, novel orthopedic biotherapies. Ther Adv Musculoskelet Dis. 2020;12: 1759720X20966135.
[20] 李明,吕厚辰,尹鹏滨,等.两种卵巢切除术式建立大鼠骨质疏松模型的优势比较[J].解放军医学院学报,2015,36(4):383-387.
[21] 何小苏.柚皮苷对绝经后骨质疏松症的成骨作用研究[D].大理:大理大学, 2019.
[22] 刘攀杰,李永贤,马延怀,等.改良式背部正中单切口入路卵巢切除术构建大鼠骨质疏松模型的研究[J].山西医科大学学报,2020,51(8):813-818.
[23] 侯佳伟. 从七次全国人口普查看我国人口发展新特点及新趋势 [J].学术论坛, 2021,44(5):1-14.
[24] PASSARELLI PC, PAGNONI S, PICCIRILLO GB, et al. Reasons for Tooth Extractions and Related Risk Factors in Adult Patients: A Cohort Study. Int J Environ Res Public Health. 2020;17(7):2575.
[25] VAN DE RIJT LJM, STOOP CC, WEIJENBERG RAF, et al. The Influence of Oral Health Factors on the Quality of Life in Older People: A Systematic Review. Gerontologist. 2020;60(5):e378-e394.
[26] LEE JH, HAN SS, LEE C, et al. Microarchitectural changes in the mandibles of ovariectomized rats: a systematic review and meta-analysis. BMC Oral Health. 2019;19(1):128.
[27] YUAN X, PEI X, ZHAO Y, et al. A Wnt-Responsive PDL Population Effectuates Extraction Socket Healing. J Dent Res. 2018;97(7):803-809.
[28] LIU Y, LI Z, ARIOKA M, et al. WNT3A accelerates delayed alveolar bone repair in ovariectomized mice. Osteoporos Int. 2019;30(9):1873-1885.
[29] CHATTERJEE M, FAOT F, CORREA C, et al. Is the Jaw Bone Micro-Structure Altered in Response to Osteoporosis and Bisphosphonate Treatment? A Micro-CT Analysis. Int J Mol Sci. 2021;22(12):6559.
[30] PATULLO IM, TAKAYAMA L, PATULLO RF, et al. Influence of ovariectomy and masticatory hypofunction on mandibular bone remodeling. Oral Dis. 2009;15(8):580-586.
[31] MA Z, LI S, SUN Y. Effect of enhanced masticatory force on OPG, RANKL and MGF in alveolar bone of ovariectomized rats. J Appl Oral Sci. 2020;28:e20190409.
[32] SUN Y, WAN B, WANG R, et al. Mechanical Stimulation on Mesenchymal Stem Cells and Surrounding Microenvironments in Bone Regeneration: Regulations and Applications. Front Cell Dev Biol. 2022;10:808303.
[33] SUN Z, HERRING SW, TEE BC, et al. Alveolar ridge reduction after tooth extraction in adolescents: an animal study. Arch Oral Biol. 2013;58(7):813-825.
[34] WHITE SC, RUDOLPH DJ. Alterations of the trabecular pattern of the jaws in patients with osteoporosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88(5):628-635.
[35] SÓ BB, SILVEIRA FM, LLANTADA GS, et al. Effects of osteoporosis on alveolar bone repair after tooth extraction: A systematic review of preclinical studies. Arch Oral Biol. 2021;125:105054.
[36] 王宁涛,李萌宇,华洪飞, 等.去卵巢骨质疏松大鼠拔牙创模型研究[J].口腔医学,2017,37(6):481-484.
[37] AN J, YANG H, ZHANG Q, et al. Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation. Life Sci. 2016;147:46-58.
[38] SHANGGUAN WJ, ZHANG YH, LI ZC, et al. Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats. Int J Mol Med. 2017;40(6):1741-1749.
[39] LI P, WU H, WANG Y, et al. Toxicological evaluation of naringin: Acute, subchronic, and chronic toxicity in Beagle dogs. Regul Toxicol Pharmacol. 2020;111:104580.
[40] ZHU Z, XIE W, LI Y, et al. Effect of Naringin Treatment on Postmenopausal Osteoporosis in Ovariectomized Rats: A Meta-Analysis and Systematic Review. Evid Based Complement Alternat Med. 2021;2021:6016874.
[41] RAMESH P, JAGADEESAN R, SEKARAN S, et al. Flavonoids: Classification, Function, and Molecular Mechanisms Involved in Bone Remodelling. Front Endocrinol (Lausanne). 2021;12:779638.
[42] LI N, JIANG Y, WOOLEY PH, et al. Naringin promotes osteoblast differentiation and effectively reverses ovariectomy-associated osteoporosis. J Orthop Sci. 2013; 18(3):478-485.
[43] GE X, ZHOU G. Protective effects of naringin on glucocorticoid-induced osteoporosis through regulating the PI3K/Akt/mTOR signaling pathway. Am J Transl Res. 2021;13(6):6330-6341.
[44] VARGAS-SANCHEZ PK, FERNANDES RR, FURLANETO FAC, et al. Osteoporosis Affects Functional Activity and Gene Expression of Osteoblastic Cells Derived from Rat Alveolar Bone. Braz Dent J. 2020;31(6):617-622.
[45] NIU Q, HE J, WU M, et al. Transplantation of bone marrow mesenchymal stem cells and fibrin glue into extraction socket in maxilla promoted bone regeneration in osteoporosis rat. Life Sci. 2022;290:119480.
[46] GENG Q, GAO H, YANG R, et al. Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence. Int J Biol Sci. 2019;15(1):58-68.
[47] TAKEGAHARA N, KIM H, CHOI Y. RANKL biology. Bone. 2022;159:116353.
[48] UDAGAWA N, KOIDE M, NAKAMURA M, et al. Osteoclast differentiation by RANKL and OPG signaling pathways. J Bone Miner Metab. 2021;39(1):19-26.
[49] YASUDA H. Anti-RANKL antibody was approved for the treatment of osteoporosis in Japan. Nihon Rinsho Meneki Gakkai Kaishi. 2013;36(4):209-216.
[50] TSUKASAKI M, ASANO T, MURO R, et al. OPG Production Matters Where It Happened. Cell Rep. 2020;32(10):108124.
[51] WU GJ, CHEN KY, YANG JD, et al. Naringin Improves Osteoblast Mineralization and Bone Healing and Strength through Regulating Estrogen Receptor Alpha-Dependent Alkaline Phosphatase Gene Expression. J Agric Food Chem. 2021;69(44):13020-13033.