研究动态
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中国画眉是通过抑制c-Fos/NFATc1信号通路调节骨吸收作用,并在卵巢切除模型中减轻骨质流失。

Gleditsiae fructus regulates osteoclastogenesis by inhibiting the c‑Fos/NFATc1 pathway and alleviating bone loss in an ovariectomy model.

发表日期:2023 Oct
作者: Chang-Young Cho, Se Hwang Kang, Byung-Chan Kim, Tae-Kyu Kim, Jae-Hyun Kim, Minsun Kim, Youngjoo Sohn, Hyuk-Sang Jung
来源: Bone & Joint Journal

摘要:

医学和经济的发展使人类寿命得以延长,全球范围内的老年人口也相应增加。骨质疏松症是一种常见的老年病,患者没有症状,即使轻微的冲击也会导致骨折,严重影响生活质量。骨质疏松症的治疗通常涉及双膦酸盐和选择性雌激素受体调节剂。然而,如果长期使用,这些治疗方法会引起严重的副作用,如下颌骨坏死和乳腺癌。因此,从具有较少副作用的天然产物中开发治疗药物至关重要。山杏子是一种干果或未成熟果实,由华山杏制成,含有各种三萜皂苷化合物。山杏子具有抗炎作用,已在多种疾病中证实,由于抗炎作用在抑制破骨细胞分化中起重要作用,因此人们预期山杏子对破骨细胞分化和绝经期骨质疏松症具有疗效;然而,据我们所知,尚未对此进行研究。因此,本研究旨在探讨山杏子对破骨细胞发生的影响,并调查其抑制破骨细胞分化的机制。采用酒石酸酪氨酸酸性磷酸酶(TRAP)染色、坑形成实验、丝状肌动蛋白(F-actin)环形成实验、免疫印迹和反转录-定量PCR分析方法,确定山杏子对破骨细胞发生的影响。此外,给绝经期骨质疏松动物模型注射山杏子,通过显微CT分析股骨的骨微结构的变化。同时进行了股骨组织和血清的评估。本研究发现,注射山杏子可以降低破骨细胞水平、F-actin环形成、TRAP活性和坑面积。此外,山杏子显示出剂量依赖的核因子激活T细胞细胞浆、c-Fos和其他与破骨细胞发生相关的标记物的抑制作用。
Medical and economic developments have allowed the human lifespan to extend and, as a result, the elderly population has increased worldwide. Osteoporosis is a common geriatric disease that has no symptoms and even a small impact can cause fractures in patients, leading to a serious deterioration in the quality of life. Osteoporosis treatment typically involves bisphosphonates and selective estrogen receptor modulators. However, these treatments are known to cause severe side effects, such as mandibular osteonecrosis and breast cancer, if used for an extended period of time. Therefore, it is essential to develop therapeutic agents from natural products that have fewer side effects. Gleditsiae fructus (GF) is a dried or immature fruit of Gleditsia sinensis Lam. and is composed of various triterpenoid saponins. The anti‑inflammatory effect of GF has been confirmed in various diseases, and since the anti‑inflammatory effect plays a major role in inhibiting osteoclast differentiation, GF was expected to be effective in osteoclast differentiation and menopausal osteoporosis; however, to the best of our knowledge, it has not yet been studied. Therefore, the present study was designed to examine the effect of GF on osteoclastogenesis and to investigate the mechanism underlying inhibition of osteoclast differentiation. The effects of GF on osteoclastogenesis were determined in vitro by tartrate‑resistant acid phosphatase (TRAP) staining, pit formation assays, filamentous actin (F‑actin) ring formation assays, western blotting and reverse transcription‑quantitative PCR analyses. Furthermore, the administration of GF to an animal model exhibiting menopausal osteoporosis allowed for the analysis of alterations in the bone microstructure of the femur using micro‑CT. Additionally, assessments of femoral tissue and serum were conducted. The present study revealed that the administration of GF resulted in a reduction in osteoclast levels, F‑actin rings, TRAP activity and pit area. Furthermore, GF showed a dose‑dependent suppression of nuclear factor of activated T‑cells cytoplasmic, c‑Fos and other osteoclastogenesis‑related markers.