Wang Yang, Li Xiaoyan, Deng Feifei, Yin Ruofeng
Department of Orthopedic Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
Department of Hospital Infection Management, Hospital of Stomatology, Jilin University, Changchun, China.
Front Pharmacol. 2021 Nov 5;12:734539. doi: 10.3389/fphar.2021.734539. eCollection 2021.
To investigate the therapeutic effect of Hydroxy-safflower yellow A (HSYA) on rat's osteoporosis and explore its potential mechanism of action. Bilateral ovariectomized female rats (OVX) were used to establish a postmenopausal rat model of osteoporosis. HSYA was given as an intervention, and estradiol was used as a positive control. The levels of serum alkaline phosphatase (ALP), calcium ion (Ca), and inorganic phosphorus (IP) were used to detect bone loss. Three months after modeling, the rats were sacrificed and the rat's ovaries, kidneys, tibia, and femur were used to calculate the organ index. The bone marrow of the femur of the rats was stained with Giemsa staining. The femur strength of rats was measured by INSTRON. The degree of osteoporosis was detected by pathological staining after decalcification of bone tissue. Predicted the main targets of HSYA in combination with bioinformatics, and the proteins related to osteoclast differentiation were detected in combination with western blotting. The effect of HSYA on the differentiation of RAW264.7 cells into osteoclasts was observed. The Giemsa staining and serum test results showed that the operation was successful and affected bone metabolism. In the bone strength test, HSYA significantly increased the maximum threshold of femoral load in rats. Pathological examination showed that tibial cartilage, trabecular bone, and cortex significantly increased after treatment with HYSA. The number of osteoblasts increased while the number of osteoclasts decreased-elevated levels of type I and III collagen. Autodock was used for molecular docking of potential targets of HSYA. qPCR and western blot were used to show that the expression levels of CA2 and osteoclast differentiation-related proteins were significantly decreased after HSYA treatment. Cell level results showed that HSYA could inhibit the activity of osteoclasts and the ability of RAW264.7 cells to differentiate into osteoclasts. HSYA can inhibit the differentiation and formation of osteoclasts by inhibiting the expression of CA2 and relieving osteoporosis symptoms in OVX rats.
探讨羟基红花黄色素A（HSYA）对大鼠骨质疏松症的治疗作用，并探究其潜在作用机制。采用双侧卵巢切除的雌性大鼠（OVX）建立绝经后骨质疏松大鼠模型。给予HSYA作为干预措施，并以雌二醇作为阳性对照。通过检测血清碱性磷酸酶（ALP）、钙离子（Ca）和无机磷（IP）水平来检测骨质流失情况。建模三个月后，处死大鼠，取大鼠卵巢、肾脏、胫骨和股骨计算器官指数。对大鼠股骨骨髓进行吉姆萨染色。采用INSTRON测定大鼠股骨强度。通过骨组织脱钙后的病理染色检测骨质疏松程度。结合生物信息学预测HSYA的主要靶点，并结合蛋白质免疫印迹法检测与破骨细胞分化相关的蛋白质。观察HSYA对RAW264.7细胞向破骨细胞分化的影响。吉姆萨染色和血清检测结果表明手术成功且影响了骨代谢。在骨强度测试中，HSYA显著提高了大鼠股骨负荷的最大阈值。病理检查显示，HSYA治疗后胫骨软骨、小梁骨和皮质显著增加。成骨细胞数量增加而成骨细胞数量减少，I型和III型胶原蛋白水平升高。采用Autodock对HSYA的潜在靶点进行分子对接。qPCR和蛋白质免疫印迹法表明，HSYA处理后CA2和破骨细胞分化相关蛋白的表达水平显著降低。细胞水平结果表明，HSYA可抑制破骨细胞活性以及RAW264.7细胞向破骨细胞分化的能力。HSYA可通过抑制CA2的表达来抑制破骨细胞的分化和形成，并缓解OVX大鼠的骨质疏松症状。
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