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骨黏连蛋白 S 和选择性结缔组织核甙酸成分对体外人破骨细胞的影响。

Effects of Osteochondrin S and select connective tissue ribonucleinate components on human osteoclasts in vitro.

机构信息

Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.

出版信息

J Pharm Pharmacol. 2013 Aug;65(8):1214-22. doi: 10.1111/jphp.12088. Epub 2013 Jun 20.

Abstract

OBJECTIVES

Osteochondrin S, a natural product derived from connective tissues and yeast, is used to treat osteoarthritis. The aim of this study was to determine the effect of Osteochondrin S on human osteoclast activity in vitro.

METHODS

Osteoclasts were derived from human peripheral blood mononuclear cells stimulated with macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B (RANK) ligand. Cells were treated with 23.5-587.2 ng/ml Osteochondrin S or 0.2-5 mg/ml of RNA components (synovia, placenta, intervertebral disc or cartilage). The effects on osteoclast formation and resorptive activity were assessed. Real-time polymerase chain reaction was conducted to assess the expression of key osteoclast genes.

KEY FINDINGS

Osteochondrin S and the individual RNA extracts resulted in a concentration-dependent inhibition of human osteoclast activity. Osteochondrin S did not affect RANK, nuclear factor of activated T cells (NFATc1), osteoclast-associated receptor or cathepsin K expression. However, there was a significant (P < 0.05) reduction in mRNA expression of calcitonin receptor. Osteochondrin S treatment also significantly increased the expression of osteoclast inhibitory factor interferon-β and, interestingly, increased the expression of tumour necrosis-α-like weak inducer of apoptosis (TWEAK).

CONCLUSIONS

Osteochondrin S inhibited the resorptive ability of osteoclasts. These actions are likely to occur at a late stage during osteoclast formation, downstream of NFATc1. Overall, the findings show that Osteochondrin S inhibition of osteoclast activity may be responsible for its beneficial effects on diseases such as osteoarthritis.

摘要

目的

来源于结缔组织和酵母的天然产物骨黏连蛋白 S 用于治疗骨关节炎。本研究旨在确定骨黏连蛋白 S 对体外人破骨细胞活性的影响。

方法

破骨细胞来源于人外周血单个核细胞,经巨噬细胞集落刺激因子和核因子κ B 受体激活剂(RANKL)刺激而成。用 23.5-587.2ng/ml 骨黏连蛋白 S 或 0.2-5mg/mlRNA 成分(滑膜、胎盘、椎间盘或软骨)处理细胞。评估对破骨细胞形成和吸收活性的影响。进行实时聚合酶链反应以评估关键破骨细胞基因的表达。

主要发现

骨黏连蛋白 S 和各个 RNA 提取物均导致人破骨细胞活性呈浓度依赖性抑制。骨黏连蛋白 S 不影响 RANK、活化 T 细胞核因子(NFATc1)、破骨细胞相关受体或组织蛋白酶 K 的表达。然而,降钙素受体的 mRNA 表达显著(P<0.05)降低。骨黏连蛋白 S 处理还显著增加了破骨细胞抑制因子干扰素-β的表达,有趣的是,增加了肿瘤坏死-α样凋亡弱诱导物(TWEAK)的表达。

结论

骨黏连蛋白 S 抑制破骨细胞的吸收能力。这些作用可能发生在 NFATc1 之后的破骨细胞形成的晚期。总的来说,这些发现表明骨黏连蛋白 S 抑制破骨细胞活性可能是其对骨关节炎等疾病有益作用的原因。

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