Influence of Local Osteoclast Activation on the Healing of Tooth Extraction Wound under Bisphosphonates Administration

doi:10.3969/j.issn.1005-4979.2018.02.002

Abstract

Abstract: Objective: The aim of this study is to explore the influence of local osteoclast activation during bisphosphonate administration on the healing of tooth extraction wound. Methods: 24 female SD rats at the age of 8-weeks were divided into experimental group and control group randomly. The first maxillary molar was extracted after 3 months of ovariectomy which followed by zoledronic acid treatment for 1 month. Gelfoam with Rankl (the receptor activator of nuclear factor-κB ligand) and M-CSF (macrophage-colony stimulating factor, M-CSF) was placed in tooth extracted socket in experimental group while gelfoam with saline for control group. The animals were sacrificed to evaluate wound healing of tooth extraction after 2 weeks. Results: Wound healing in the experimental group was better than that in the control group. The histological staining displayed more osteogenesis in the experimental group followed by increased number of osteoclast showed by TRAP staining. Immunohistochemical staining revealed a stronger bone formation ability(opn and dmp1) in experimental group. Conclusion: Activated osteoclasts can promote the healing of tooth extracted socket after the application of bisphosphonates.

Key words: bisphosphonate, osteoclast, tooth extraction, bone remodeling

摘要： 目的：通过动物模型，研究局部激活破骨细胞对应用双膦酸盐后拔牙创愈合的影响，以期找到预防双膦酸盐相关性颌骨坏死的方法。方法：选用24只8周龄雌性SD大鼠随机分为实验组和对照组，行双侧卵巢切除术(ovariectomy ,OVX)，术后3个月开始应用双膦酸盐。用药一个月后，拔除大鼠左侧上颌第一磨牙。实验组拔牙创内放置含有巨噬细胞集落刺激因子（macrophage-colony stimulating factor, M-CSF）与核因子-κB受体活化因子配体（the receptor activator of nuclear factor-κB ligand, Rankl）的明胶海绵，对照组放置含有生理盐水的明胶海绵。拔牙后2周，收取样本，评价拔牙创愈合情况。结果：TRAP染色结果显示实验组牙槽窝内的破骨细胞数量较对照组明显增多。免疫组织化学染色结果显示实验组成骨能力标记物骨桥蛋白（osteopontin，OPN）、牙本质基质蛋白1（dentin matrix protein 1，DMP1）表达量增加。组织学检测结果显示实验组拔牙创牙槽窝新生骨质较对照组明显增多。结论：局部激活破骨细胞可以促进应用双膦酸盐后的拔牙创愈合。

关键词: 双膦酸盐； , 破骨细胞； , 牙拔除术； , 颌骨坏死

CLC Number:

R782.1

WAN Hui-xuan, CAI Ming-xiang, SUN Yao. Influence of Local Osteoclast Activation on the Healing of Tooth Extraction Wound under Bisphosphonates Administration[J]. 《Journal of Oral and Maxillofacial Surgery》, doi: 10.3969/j.issn.1005-4979.2018.02.002.

万会璇，蔡明详，孙瑶. 局部激活破骨细胞对大鼠应用双膦酸盐后拔牙创愈合的影响[J]. 《口腔颌面外科杂志》, doi: 10.3969/j.issn.1005-4979.2018.02.002.

/ / Recommend / Download Citations

URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.3969/j.issn.1005-4979.2018.02.002

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2018/V28/I2/65

References

[1] Fliefel R, Troltzsch M, Kühnisch J, et al. Treatmentstrategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review[J]. Int J Oral Maxillofac Surgery, 2015, 44(5):568-85.
[2] Zhang J, Park J, Lee J W, et al. Bisphosphonates hinder osteoblastic/osteoclastic differentiation in the maxillary sinus mucosa-derived stem cells[J]. Clinical Oral Investigations, 2017:1-11.
[3] Ikeda T, Kuraguchi J, Kogashiwa Y, et al. Successful treatment of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) patients with sitafloxacin: New strategies for the treatment of BRONJ[J]. Bone, 2015, 73:217-222.
[4] Marx R E. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic[J]. J Oral Maxillofac Surgery, 2003, 61(9):1115-1117.
[5] Zhang X, Hamadeh I S, Song S, et al. Osteonecrosis of the jaw in the United States food and drug administration's adverse event reporting system(FAERS)[J]. J Bone Mineral Res, 2016, 31(2):336-340.
[6] Asagiri M, Takayanagi H. The molecular understanding of osteoclast differentiation[J]. Bone, 2007, 40(2):251-64.
[7] Kylmaoja E, Nakamura M, Tuukkanen J. Osteoclasts and remodeling based bone formation[J]. Curr Stem Cell Res Ther, 2016, 11(8):626-633.
[8] Teitelbaum S L, Ross F P. Genetic regulation of osteoclast development and function[J]. Nature Reviews Genetics, 2003, 4(8):638-49.
[9] Park J H, Lee N K, Lee S Y. Current Understanding of RANK signaling in osteoclast differentiation and maturation[J]. Molecules Cells, 2017, 40(10):706-713.
[10] Zaidi M. Skeletal remodeling in health and disease[J]. Nature Med, 2007, 13(7):791-801.
[11] Sims N A, Martin T. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit[J]. Bonekey Reports, 2014, 3:481.
[12] Jiménez-Ortega R F, Ramírez-Salazar E G, Parra-Torres A Y, et al. Identification of microRNAs in human circulating monocytes of postmenopausal osteoporotic Mexican-Mestizo women: a pilot study[J]. Exp Ther Med 2017, 14(6):5464-5472.
[13] Sawatari Y, Marx R E. Bisphosphonates and bisphosphonate induced osteonecrosis.[J]. Oral Maxillofac Surg Clin North Am, 2007, 19(4):487-498.
[14] Salvatore L, Ruggiero DMD MD, Thomas B, et al. American association of oral and maxillofacial surgeons position paper on bisphosphonate-related osteonecrosis of the jaw-2009 update[J]. Aust Endod J, 2009, 35(3):119-130.
[15] Hamadeh I S, Ngwa B A, Gong Y. Drug induced osteonecrosis of the jaw[J]. Cancer Treat Rev, 2015, 41(5):455-464
[16] Franco-pretto E, Pacheco M, Moreno A, et al. Bisphosphonate-induced osteonecrosis of the jaws: clinical, imaging, and histopathology findings[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2014, 118(4):408-417.
[17] Xue G, Yu W, Zhao H, et al. Skeletal site-specific effects of zoledronate on in vivo bone remodeling and in vitro BMSCs osteogenic activity[J]. Sci Rep, 2017, 7:36129.
[18] Gao S Y, Zheng G S, Wang L, et al. Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB[J]. Plos One, 2017, 12(6):e0179248.
[19] Molon R S D, Cheong S, Bezouglaia O, et al. Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: a novel ONJ mouse model[J]. Bone, 2014, 68:11-19.
[20] Borromeo G L, Brand C, Clement J G, et al. A Large case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw[J]. J Bone Mineral Research, 2014, 29(6):1363-8.
[21] Di Nisco C, Zizzari V L, Zara S, et al. RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects[J]. Eur J Histochem, 2015, 59(1):2455.
[22] Tsubaki M, Komai M, Itoh T, et al. Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation[J]. J Biomed Sci, 2014, 21(1):10.
[23] Pan B, Farrugia AN, To LB, et al. The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE)[J]. J Bone Miner Res, 2004, 19(1):147-154.

Please choose a citation manager

Content to export