Effect of Ovariectomy on Macrophage Polarization in Bone Marrow: A Pilot Study in Mice

doi:10.13701/j.cnki.kqyxyj.2020.12.016

Abstract

Abstract: Objective: To investigate the role of estrogen in regulating macrophage polarization by establishing a model of osteoporosis in ovariectomized mice. Methods: 8-week-old healthy female C57BL/6 mice were randomly divided into ovariectomy group and control (pseudo-surgical) group. Body weights were measured every 3 days and animals were euthanized at 12-week-old. Bone mineral density was measured using DXA. Serum interleukin-10 concentration was determined by ELISA. Bone marrow cells were obtained from femoral bone and macrophages polarization were determined using flow cytometry. The ratio of M1/M2 in the ovariectomy group was compared to that of control group. Macrophage cells were cultured in vitro in the presence of IL-10 and the expression of M1/M2 related genes was detected using realtime-PCR. Results: Bone density measurement confirmed that ovariectomy induced bone loss in the femur (P<0.05). The ovariectomy group mice gained weight for 18 days. Ovariectomy group show significantly reduced serum IL-10 (P<0.01) and bone marrow cells IL-10 mRNA expression (P<0.01), and increased M1 to M2 macrophages ratio (P<0.01). Mechanically, in vitro macrophage cell culture experiment confirmed that IL-10 induced upregulation of M2 macrophage-related genes (P<0.01). Conclusion: Insufficient estrogen secretion lowers serum IL-10 expression and bone marrow cells IL-10 mRNA expression, which enables macrophage differentiation toward M1 type.

Key words: osteoporosis, macrophage, polarization, IL-10

LUO Tao, ZHENG Zhichao, HUANG Jiangyong, GUO Lvhua, WU Zhe, ZHANG Qingbin. Effect of Ovariectomy on Macrophage Polarization in Bone Marrow: A Pilot Study in Mice[J]. Journal of Oral Science Research, 2020, 36(12): 1153-1156.

References

[1] 吴晓玲,郑茜,吕佳岭,等.雌激素微环境下非经典Wnt/Ca~(2+)信号通路调控人牙周膜干细胞成骨分化的研究[J].口腔医学研究,2019,35(1):33-37.
[2] 周玲.低水平雌激素对大鼠骨髓巨噬细胞生物学活性的影响[C].第十三次全国老年口腔医学学术年会论文汇编,2018:192-194.
[3] Streicher C, Heyny A, Andrukhova O, et al. Estrogen regulates bone turnover by targeting RANKL expression in bone lining cells [J]. Sci Rep, 2017,7(1):6460.
[4] Eyster KM. The estrogen receptors: an overview from different perspectives [J]. Methods Mol Biol, 2016, 1366:1-10.
[5] Streicher C, Heyny A, Andrukhova O, et al. Estrogen regulates bone turnover by targeting RANKL expression in bone lining cells [J]. Sci Rep, 2017, 7(1):6460.
[6] Srivastava RK, Dar HY, Mishra PK. Immunoporosis: immunology of osteoporosis-role of T cells [J]. Front Immunol, 2018,9:657.
[7] Teitelbaum SL. Bone resorption by osteoclasts [J]. Science, 2000,289( 5484): 1504-1508.
[8] Benjamin PS, Allison RP, Laurie KM. Macrophages: their emerging roles in bone [J]. J Bone Miner Res, 2015, 30(12):2140-2149.
[9] Das A, Sinha M, Datta S, et al. Monocyte and macrophage plasticity in tissue repair and regeneration [J]. Am J Pathol, 2015, 185(10): 2596-2606.
[10] Mills CD. Anatomy of a discovery: m1 and m2 macrophages [J]. Front Immunol, 2015, 6: 212.
[11] Kubatzky KF, Uhle F, Eigenbrod T. From macrophage to osteoclast-How metabolism determines function and activity [J]. Cytokine, 2018, 112:102-115.
[12] Yeon JT, Choi SW, Kim SH. Arginase 1 is a negative regulator of osteoclast differentiation [J]. Amino Acids, 2016, 48(2):559-565.
[13] Lopes RL, Borges TJ, Zanin RF, et al. IL-10 is required for polarization of macrophages to M2-like phenotype by mycobacterial DnaK (heat shock protein 70) [J]. Cytokine, 2016, 85:123-129.

[1]	YANG Lei, GUO Liuyun, CHENG Zhifen, LI Bihao. Correlation between Shh Protein and Inflammatory Degree of Chronic Periodontitis [J]. Journal of Oral Science Research, 2020, 36(2): 131-134.
[2]	ZHANG Xiaoyan, LIU Yunxin, WU Tie. Effects of Tanshinol on RANKL/OPG of Alveolar Osteoblasts [J]. Journal of Oral Science Research, 2019, 35(9): 894-897.
[3]	XIN Xirui, ZHOU Yanmin. Research Progress of Simvastatin in Promoting Osseointegration and Improving Poor Osteogenic Conditions [J]. Journal of Oral Science Research, 2019, 35(8): 734-737.
[4]	SUN Hong-chen, LI Xing. Advances in Nanomedicine Strategies to Target Tumor-associated Macrophage [J]. Journal of Oral Science Research, 2019, 35(6): 511-516.
[5]	FENG Li-hua, WANG Min, XIA Hai-bin, HUANG Kai-yao. Effect of Osteopontin on Polarization of Macrophage in Vitro. [J]. Journal of Oral Science Research, 2019, 35(5): 497-501.
[6]	PENG Shuang-lin, YAO Zhi-hao, LUO Dao-wen, YANG Shuang-lin, LI Yong, XIAO Jin-gang. Experimental Study on Repair of Critical-size Calvarial Defects in Osteoporotic Rats by Biphasic Calcium Phosphate Ceramic Scaffold [J]. Journal of Oral Science Research, 2019, 35(4): 377-381.
[7]	WANG Jia, ZHANG Wenjing, HAN Xiangzhen, ZHOU Qiqi, HE Huiyu. Effect of Macrophage Colony-Stimulating Factor Overexpression on Osteoclast-related Cytokine Factors [J]. Journal of Oral Science Research, 2019, 35(11): 1089-1093.
[8]	ZHONG Xing-hua, LI Hao, LI Wei. Effects of AhR Overexpression on the Porphyromonas gingivalis Lipopolysaccharide- caused Inflammatory Response of Macrophages under High Glucose Conditions. [J]. Journal of Oral Science Research, 2018, 34(12): 1329-1332.
[9]	WANG Liu-ran, LIU Xin-chan, MENG Yang, DING Xiao-han, WU Zhou, YU Wei-xian. Study on Mongersen's Anti-inflammatory Effect in Periodontal Inflammatory Microenvironment in Vitro. [J]. Journal of Oral Science Research, 2018, 34(12): 1333-1336.
[10]	WANG Mi, GAO Ying, YAN Wen-ting, ZHOU Gen-xiang, LIU Xia-qing.. Effect of Metformin on Advanced Glycation End Products in Ovariectomized Rats. [J]. Journal of Oral Science Research, 2017, 33(5): 479-481.
[11]	GUAN Xiao-yue, QIAN Hua, BIAN Zhuan.. Study of Follicle Stimulating Hormone(FSH) in Postmenopausal-osteoporosis and Oral Bone Resorption Disease. [J]. Journal of Oral Science Research, 2017, 33(5): 574-576.
[12]	ZHANG Yu, LIN JIU, GAO Wei, HU Yi, GAO Yi, XIONG Wen-bi, PAN Jian.. Effects of Daidzein on Bone Rebuiling of Alveolar Fossa after Tooth Extraction in Osteoporotic-model Rats. [J]. Journal of Oral Science Research, 2017, 33(3): 258-261.
[13]	WANG Peng, HE Dong-ming, LIU Biao, HU Jing, LI Ji-hua, LI Yun-feng.. SEMA3A Suspended in Matrigel Improves Titanium Implant Fixation in Ovariectomized Rats. [J]. Journal of Oral Science Research, 2017, 33(2): 127-131.
[14]	SHEN Su-qian, LI Juan, HUANG Shi-guang. Expression of Stem Cell Factor in the Periapical Tissues of Human Chronic Periapical Diseases. [J]. Journal of Oral Science Research, 2017, 33(2): 179-182.
[15]	LI Ge-ge, TANG Qiu-ling, PAN Jia-hui, WANG Liu-ran, MENG Yang, YUE Yi-yun, DING Xiao-han, LIU Dong-ning, YU Wei-xian. Study on Anti-inflammatory Effects of PMX205 in Vitro [J]. Journal of Oral Science Research, 2017, 33(12): 1246-1249.