Oxyresveratrol attenuates bone resorption by inhibiting the mitogen-activated protein kinase pathway in ovariectomized rats

IF 3.9 2区医学 Q2 NUTRITION & DIETETICS

Nutrition & Metabolism Pub Date : 2024-01-19 DOI:10.1186/s12986-024-00781-4

Yea-Jin Lee, Jin-Chul Ahn, Chung-Hun Oh

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引用次数: 0

Abstract

Bone is continuously produced by osteoblasts and resorbed by osteoclasts to maintain homeostasis. Impaired bone resorption by osteoclasts causes bone diseases such as osteoporosis and arthritis. Most pharmacological treatment of osteoporosis focuses on inhibiting osteoclast differentiation, often to restore osteoclast/osteoclast balance. However, recent osteoporosis treatments have various side effects. According to a recent study, resveratrol, known as a stilbenoid family, is known to increase bone density, and the osteoclast inhibitory effect was confirmed using oxyresveratrol, a stilbenoid family. Here, we investigated the effect of oxyresveratrol on osteoclast differentiation and an ovariectomized mouse model. Mouse leukemia monocyte/macrophage cell line RAW 264.7 was treated with oxyresveratrol, and cell cytotoxicity was confirmed by measuring MTT assay. Tartrate-resistant acid phosphatase (TRAP), an enzyme marker for osteoclasts, was confirmed by staining. In addition, osteoclast differentiation markers and MAPK-related markers were confirmed at the mRNA level and protein expression. The effect of oxyresveratrol was confirmed using ovariectomized mice. Deoxypyridinoline (DPD) was measured using mouse urine and TRAP activity was observed using serum. Bone mineral density was also measured using Micro-CT. The polyphenol oxyresveratrol inhibited receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells. Furthermore, oxyresveratrol inhibited TRAP activity and actin-ring formation. Moreover, oxyresveratrol suppressed the phosphorylation of the RANKL-induced mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK and significantly reduced the expression of bone differentiation markers (NFATc1, cathepsin K, and TRAP). Oxyresveratrol inhibits osteoclast differentiation via MAPK and increases bone density in ovariectomized rats, suggesting it has therapeutic potential for bone diseases such as osteoporosis. We confirmed the osteoporosis prevention effect of OR in Raw 264.7 cells, and future studies should confirm the effect of OR using rat bone marrow-derived cells.

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氧白藜芦醇通过抑制卵巢切除大鼠的丝裂原活化蛋白激酶通路来减轻骨吸收

骨骼不断由成骨细胞生成，并由破骨细胞吸收，以维持体内平衡。破骨细胞的骨吸收功能受损会导致骨质疏松症和关节炎等骨病。大多数骨质疏松症的药物治疗都侧重于抑制破骨细胞的分化，通常是为了恢复破骨细胞/破骨细胞的平衡。然而，最近的骨质疏松症治疗方法有各种副作用。根据最近的一项研究，白藜芦醇（被称为白藜芦醇家族）具有增加骨密度的作用，而使用白藜芦醇家族中的氧白藜芦醇则证实了其抑制破骨细胞的作用。在此，我们研究了氧白藜芦醇对破骨细胞分化和卵巢切除小鼠模型的影响。用氧白藜芦醇处理小鼠白血病单核/巨噬细胞系 RAW 264.7，并通过 MTT 试验确认细胞毒性。抗酒石酸磷酸酶（TRAP）是破骨细胞的酶标记物，通过染色得到了证实。此外，破骨细胞分化标志物和 MAPK 相关标志物的 mRNA 水平和蛋白表达也得到了证实。使用卵巢切除的小鼠证实了氧白藜芦醇的作用。利用小鼠尿液测定了脱氧吡啶啉（DPD），利用血清观察了 TRAP 活性。此外，还使用 Micro-CT 测量了骨矿密度。多酚氧白藜芦醇可抑制核因子卡帕Β配体受体激活剂（RANKL）诱导的 RAW 264.7 细胞破骨细胞分化。此外，氧白藜芦醇还能抑制 TRAP 活性和肌动蛋白环的形成。此外，氧白藜芦醇还抑制了 RANKL 诱导的丝裂原活化蛋白激酶（MAPKs）p38、JNK 和 ERK 的磷酸化，并显著降低了骨分化标志物（NFATc1、cathepsin K 和 TRAP）的表达。氧白藜芦醇可通过 MAPK 抑制破骨细胞分化，增加卵巢切除大鼠的骨密度，这表明它对骨质疏松症等骨科疾病具有治疗潜力。我们在 Raw 264.7 细胞中证实了氧白藜芦醇预防骨质疏松症的作用，未来的研究应使用大鼠骨髓衍生细胞证实氧白藜芦醇的作用。

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来源期刊

Nutrition & Metabolism 医学-营养学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects. The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases. Key areas we wish to encourage submissions from include: -how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes; -the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components; -how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved; -how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.