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线抑制破骨细胞分化,并抑制去卵巢诱导骨质疏松模型中骨密度的降低。

Line inhibits osteoclast differentiation and suppresses bone mineral density reduction in the ovariectomy‑induced osteoporosis model.

机构信息

Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02‑447, Republic of Korea.

出版信息

Mol Med Rep. 2021 Aug;24(2). doi: 10.3892/mmr.2021.12246. Epub 2021 Jun 29.

Abstract

Bone homeostasis is maintained by osteoclasts that absorb bone and osteoblasts that form bone tissue. Menopausal osteoporosis is a disease associated with aging and hormonal changes due to menopause causing abnormal activation of osteoclasts, resulting in a decrease in bone density. Existing treatments for osteoporosis have been reported to have serious side effects, such as jawbone necrosis and breast and uterine cancer; therefore, their use by patients is decreasing, whilst studies focusing on alternative treatments are increasingly popular. Line (SL) has been used as a medicinal plant that possesses several pharmacological effects, such as anti‑inflammatory and hepatotoxic protective effects. To the best of our knowledge, however, its effects on osteoporosis and osteoclasts have not been demonstrated previously. In the present study, the anti‑osteoporotic effect of SL was investigated using a postmenopausal model of osteoporosis in which Sprague‑Dawley rat ovaries were extracted. In addition, the inhibitory effects on osteoclast differentiation and function of SL was confirmed using an osteoclast model treated with receptor activator of NF‑κB ligand (RANKL) on murine RAW 264.7 macrophages. experiments showed that SL reduced the decrease in bone mineral density and improved changes in the morphological index of bone microstructure, such as trabecular number and separation. In addition, the number of tartrate resistant acid phosphatase‑positive cells in the femur and the expression levels of nuclear factor of activated T‑cells cytoplasmic 1 (NFATc1) and cathepsin K protein were inhibited. , SL suppressed RANKL‑induced osteoclast differentiation and bone resorption ability; this was mediated by NFATc1/c‑Fos, a key transcription factor involved in osteoclast differentiation, ultimately inhibiting expression of various osteoclast‑associated genes. These experimental results show that SL may be an alternative treatment for osteoporosis caused by abnormal activation of osteoclasts in the future.

摘要

骨稳态由吸收骨的破骨细胞和形成骨组织的成骨细胞维持。绝经后骨质疏松症是一种与衰老和绝经引起的激素变化相关的疾病,导致破骨细胞异常激活,从而导致骨密度降低。据报道,现有的骨质疏松症治疗方法有严重的副作用,如颌骨坏死以及乳腺癌和子宫癌;因此,患者的使用量正在减少,而专注于替代治疗的研究越来越受欢迎。

贯叶连翘已被用作一种药用植物,具有多种药理作用,如抗炎和肝毒性保护作用。然而,据我们所知,其以前并未显示出对骨质疏松症和破骨细胞的作用。在本研究中,使用 Sprague-Dawley 大鼠卵巢切除的绝经后骨质疏松症模型研究了贯叶连翘的抗骨质疏松作用。此外,使用核因子κB 受体激活剂配体(RANKL)处理的鼠 RAW 264.7 巨噬细胞的破骨细胞模型证实了贯叶连翘对破骨细胞分化和功能的抑制作用。

实验结果表明,贯叶连翘可减少骨密度的降低并改善骨微结构形态指数的变化,如小梁数量和分离。此外,还抑制了股骨中抗酒石酸酸性磷酸酶阳性细胞的数量以及核因子活化 T 细胞细胞质 1(NFATc1)和组织蛋白酶 K 蛋白的表达水平。

综上所述,贯叶连翘抑制了 RANKL 诱导的破骨细胞分化和骨吸收能力;这是通过 NFATc1/c-Fos 介导的,NFATc1/c-Fos 是参与破骨细胞分化的关键转录因子,最终抑制了各种破骨细胞相关基因的表达。这些实验结果表明,贯叶连翘可能成为未来异常激活破骨细胞引起的骨质疏松症的替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1415/8240179/10664916bf93/mmr-24-02-12246-g00.jpg

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