Effect of endothelial Piezo1 knockout on steroid-induced osteonecrosis of the femoral head in mice

doi:10.12307/2022.1026

Abstract

Abstract: BACKGROUND: One of the important causes of steroid-induced osteonecrosis of the femoral head is the damage of vascular endothelial cells caused by glucocorticoids, which subsequently leads to ischemia and hypoxia of the femoral head. Piezo1 plays an important role in promoting angiogenesis and homeostasis. However, the effect of endothelial Piezo1 on steroid-induced osteonecrosis of the femoral head is unclear.
OBJECTIVE: To observe the effects of endothelial Piezo1 on steroid-induced osteonecrosis of the femoral head.
METHODS: Then male Piezo1fl/fl mice, 8 weeks of age, were randomly divided into two groups: control group and model group. Five male Piezo1ΔEC mice were selected in an experimental group, in which lipopolysaccharide at a dose of 20 μg/kg was intraperitoneally injected for 2 continuous days, followed by intramuscular injection of methylprednisolone sodium succinate 40 mg/kg for 4 weeks. The control group was injected with the same amount of PBS at the same site. Mice were sacrificed at 12 weeks of age and bone samples of both lower limbs were obtained. Micro-CT and hematoxylin-eosin staining were used to observe and analyze the changes of bone microstructure and histomorphological changes of the femoral head in each group, and then SPSS software was used for statistical analysis.
RESULTS AND CONCLUSION: Compared with the model group, the damage of bone microstructure was significantly aggravated in the experimental group. Pathological findings further showed that the number of empty bone lacunae was significantly increased in the experimental group compared with the model group. Several bone morphometric parameters like trabecular bone volume and trabecular number were significantly reduced (P < 0.001) and trabecular separation increased significantly in the experimental group compared with the model group (P < 0.000 1). To conclude, endothelial Piezo1 can participate in the process of steroid-induced osteonecrosis of the femoral head in mice and endothelial Piezo1 gene deletion can aggravate steroid-induced osteonecrosis of the femoral head in mice.

Key words: Piezo1, steroid-induced osteonecrosis of the femoral head, Micro-CT, bone microarchitecture, mouse

CLC Number:

Pan Zhaofeng, Yang Junzheng, He Qi, Zhang Gangyu, Xiao Jiacong, Chen Baihao, Wang Haibin, Chen Peng. Effect of endothelial Piezo1 knockout on steroid-induced osteonecrosis of the femoral head in mice[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(32): 5107-5111.

Figures/Tables 3

References

[1] MALIZOS KN, KARANTANAS AH, VARITIMIDIS SE, et al.Osteonecrosis of the femoral head: etiology, imaging and treatment. Eur J Radiol. 2007;63(1):16-28.
[2] TAN G, KANG PD, PEI FX. Glucocorticoids affect the metabolism of bone marrow stromal cells and lead to osteonecrosis of the femoral head: a review. Chin Med J (Engl). 2012;125(1):134-139.
[3] ZHAO DW, YU M, HU K, et al. Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population: Results from a Nationally Representative Survey. Chin Med J (Engl). 2015;128(21):2843-2850.
[4] HYMAN AJ, TUMOVA S, BEECH DJ. Piezo1 Channels in Vascular Development and the Sensing of Shear Stress. Curr Top Membr. 2017; 79:37-57.
[5] COSTE B, MATHUR J, SCHMIDT M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330(6000):55-60.
[6] COSTE B, MURTHY SE, MATHUR J, et al. Piezo1 ion channel pore properties are dictated by C-terminal region. Nat Commun. 2015;6: 7223.
[7] WU J, LEWIS AH, GRANDL J. Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels. Trends Biochem Sci. 2017;42(1):57-71.
[8] CHEN P, ZHANG G, JIANG S, et al. Mechanosensitive Piezo1 in endothelial cells promotes angiogenesis to support bone fracture repair [published online ahead of print, 2021 Jun 7]. Cell Calcium. 2021;97:102431.
[9] CHANG C, GREENSPAN A, GERSHWIN ME. The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis. J Autoimmun. 2020;110:102460.
[10] 王傲. 激素性股骨头坏死发病机制的研究进展[J]. 中国骨与关节损伤杂志,2016,31(4):445-446.
[11] 费腾,阎作勤. 激素性股骨头坏死发病机制的研究进展[J]. 中华关节外科杂志(电子版),2011,5(4):504-508.
[12] 赵钟涵,杜玉香,张玲莉. 机械敏感性离子通道蛋白Piezo1响应力学刺激的研究进展[J]. 生命的化学,2021,41(4):804-811.
[13] LI J, HOU B, TUMOVA S, et al. Piezo1 integration of vascular architecture with physiological force. Nature. 2014;515(7526):279-282.
[14] ALBUISSON J, MURTHY SE, BANDELL M, et al. Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels [published correction appears in Nat Commun. 2013;4:2440]. Nat Commun. 2013;4:1884.
[15] 黄鹏,尚画雨,李顺昌,等. 机械敏感离子通道Piezo1在心血管系统中的作用[J]. 生命的化学,2020,40(3):369-377.
[16] CAHALAN SM, LUKACS V, RANADE SS, et al. Piezo1 links mechanical forces to red blood cell volume. Elife. 2015;4:e07370.
[17] ZENG WZ, MARSHALL KL, MIN S, et al. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science. 2018; 362(6413):464-467.
[18] 吴霁,李萍. Piezo1离子通道在心血管病中的作用[J]. 中华高血压杂志,2021,29(3):228-232.
[19] ALBARRÁN-JUÁREZ J, IRING A, WANG S, et al. Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation. J Exp Med. 2018;215(10):2655-2672.
[20] 赵璨. 机械敏感离子通道Piezo1与小鼠胰岛素抵抗的相关性及可能的炎症机制[D]. 南京:南京医科大学,2019.
[21] RETAILLEAU K, DUPRAT F, ARHATTE M, et al. Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling. Cell Rep. 2015;13(6):1161-1171.
[22] 刘蕾. 注射用血栓通抗血小板聚集及改善血流效应机制研究[D].北京:中国中医科学院,2020.
[23] SUGIMOTO A, MIYAZAKI A, KAWARABAYASHI K, et al. Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells. Sci Rep. 2017;7(1):17696.
[24] SYEDA R, XU J, DUBIN AE, et al. Chemical activation of the mechanotransduction channel Piezo1. Elife. 2015;4:e07369.
[25] WANG L, YOU X, LOTINUN S, et al. Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk. Nat Commun. 2020;11(1):282.
[26] ZARYCHANSKI R, SCHULZ VP, HOUSTON BL, et al. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood. 2012;120(9):1908-1915.
[27] JUSTESEN J, STENDERUP K, EBBESEN EN, et al. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001;2(3):165-171.