背景:骨由成骨细胞连续产生并被破骨细胞吸收以维持体内平衡。破骨细胞的骨吸收受损导致骨疾病如骨质疏松症和关节炎。大多数骨质疏松症的药物治疗集中在抑制破骨细胞分化,通常恢复破骨细胞/破骨细胞平衡。然而,最近的骨质疏松症治疗有各种副作用。根据最近的一项研究,白藜芦醇,被称为stilbenoid家族,已知会增加骨密度,使用氧化白藜芦醇证实了破骨细胞的抑制作用,一个stilbenoid家族。这里,我们研究了白藜芦醇对破骨细胞分化的影响和去卵巢小鼠模型。
方法:用白藜芦醇处理小鼠白血病单核细胞/巨噬细胞系RAW264.7,细胞毒性通过MTT测定证实。抗酒石酸酸性磷酸酶(TRAP),破骨细胞的酶标记物,通过染色证实。此外,在mRNA水平和蛋白质表达上证实了破骨细胞分化标记和MAPK相关标记。使用卵巢切除的小鼠证实了白藜芦醇的作用。使用小鼠尿液测量脱氧吡啶啉(DPD),并使用血清观察TRAP活性。还使用Micro-CT测量骨矿物质密度。
结果:多酚白藜芦醇抑制核因子κ-Β受体活化因子配体(RANKL)诱导的RAW264.7细胞的破骨细胞分化。此外,氧化白藜芦醇抑制TRAP活性和肌动蛋白环形成。此外,氧化白藜芦醇抑制RANKL诱导的丝裂原活化蛋白激酶(MAPK)p38,JNK的磷酸化,和ERK,并显着降低骨分化标志物(NFATc1,组织蛋白酶K,和陷阱)。
结论:氧化白藜芦醇通过MAPK抑制破骨细胞分化,增加去卵巢大鼠的骨密度,这表明它对骨质疏松等骨骼疾病有治疗潜力。我们证实了OR在Raw264.7细胞中的骨质疏松症预防作用,未来的研究应该证实使用大鼠骨髓来源细胞的OR的效果。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.