在卵巢切除大鼠骨质疏松症模型中,β-catenin 在塞马鲁肽的骨质保护作用中的关键作用

Mohannad Hakam Hamed Abo-Elenin, Rehab Kamel, Shahira Nofal, Amany Ali Eissa Ahmed
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摘要

绝经后骨质疏松症是一种常见的慢性内科疾病,是由于雌激素缺乏引起的骨吸收和骨形成之间的不平衡以及微结构退化造成的,通常还伴有体重增加、抑郁和失眠等其他病症。塞马鲁肽(SEM)是最近推出的一种 GLP-1 受体激动剂(GLP-1RA),可通过减轻胰岛素抵抗来治疗肥胖症和 2 型糖尿病。研究发现,GLP-1 的有益作用与脂肪分解、脂肪生成和抗炎过程的改变有关。GLP-1 类似物可直接向脂肪组织传递信号。间充质干细胞(MSCs)是源自骨髓的多学科细胞,可迁移到损伤部位并促进骨再生。间充质干细胞可分化为成骨细胞、脂肪细胞和软骨细胞。我们的目的是研究塞马鲁肽对骨形成和Wnt信号通路的作用。通过卵巢切除术诱发雌性大鼠骨质疏松症,切除卵巢的大鼠口服阿仑膦酸钠作为标准治疗,剂量为3毫克/千克,同时口服两种剂量(150微克/千克和300微克/千克)的塞马鲁肽,连续治疗10周。塞马鲁肽能改善卵巢切除术引起的骨质破坏性变化。它能改善骨的微观结构并保护骨矿物质含量。塞马鲁肽可改善卵巢切除术诱发的骨质疏松症,增加β-catenin的表达,从而增加骨形成,阻止核因子卡帕Β配体受体激活剂(RANKL)的激活。塞马鲁肽可能通过激活Wnt信号转导和减少骨吸收,可用作骨质疏松症的潜在预防和治疗药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The crucial role of beta-catenin in the osteoprotective effect of semaglutide in an ovariectomized rat model of osteoporosis

The crucial role of beta-catenin in the osteoprotective effect of semaglutide in an ovariectomized rat model of osteoporosis

Postmenopausal osteoporosis is a common chronic medical illness resulting from an imbalance between bone resorption and bone formation along with microarchitecture degeneration attributed to estrogen deficiency and often accompanied by other medical conditions such as weight gain, depression, and insomnia. Semaglutide (SEM) is a recently introduced GLP-1 receptor agonist (GLP-1RA) for the treatment of obesity and type 2 diabetes mellitus by mitigating insulin resistance. It has been discovered that the beneficial effects of GLP-1 are associated with alterations in lipolysis, adipogenesis, and anti-inflammatory processes. GLP-1 analogs transmit signals directly to adipose tissue. Mesenchymal stem cells (MSCs) are multidisciplinary cells that originate from bone marrow, migrate to injury sites, and promote bone regeneration. MSCs can differentiate into osteoblasts, adipose cells, and cartilage cells. Our aim is to investigate the role of semaglutide on bone formation and the Wnt signaling pathway. Osteoporosis was induced in female rats by ovariectomy, and the ovariectomized rats were treated with alendronate as standard treatment with a dose of 3 mg/kg orally and semaglutide with two doses (150 mcg/kg and 300 mcg/kg) S.C. for 10 successive weeks. Semaglutide ameliorates bone detrimental changes induced by ovariectomy. It improves bone microarchitecture and preserves bone mineral content. Semaglutide ameliorates ovariectomy-induced osteoporosis and increases the expression of β-catenin, leading to increased bone formation and halted receptor activator of nuclear factor kappa-Β ligand (RANKL’s) activation. Semaglutide can be used as a potential prophylactic and therapeutic drug against osteoporosis, possibly by activating Wnt signaling and decreasing bone resorption.

Graphical Abstract

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