人脱落乳牙干细胞分泌的因子通过激活内源性抗氧化系统抑制破骨细胞的形成。

IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Cheng Ding , Noboru Hashimoto , Fumiya Kano , Hirofumi Tenshin , Takahiro Arai , Linze Xia , Yang Xu , Houjun Lao , Yifei Wang , Tomonori Iwasaki , Hideharu Hibi , Akihito Yamamoto
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引用次数: 0

摘要

目的:在类风湿关节炎、骨质疏松症和骨关节炎小鼠模型中,系统给药人脱落乳牙干细胞条件培养基(CM)可抑制过度的破骨细胞活性并恢复骨完整性。然而,SHED-CM调节破骨细胞发生的机制在很大程度上仍然未知。在本研究中,我们考察了SHED-CM的体外抗破骨机制。方法:用核因子κ κ受体激活剂-Β配体(RANKL)在骨髓间充质干细胞(BMSC-CM)的shd -CM或CM存在下作用于骨髓巨噬细胞和RAW264.7细胞。通过抗酒石酸酸性磷酸酶染色、肌动蛋白环形成和破骨细胞特异性标志物的表达来评估破骨细胞的分化。rankl诱导的活性氧(ROS)的产生被分析为破骨细胞发生的关键介质。采用反转录定量PCR检测内源抗氧化基因表达的激活情况。利用液相色谱-串联质谱法(LC-MS)鉴定SHED-CM中富集的蛋白,并利用中和抗体评价其功能作用。结果:与BMSC-CM相比,SHED-CM能有效抑制rankl诱导的早期破骨细胞分化和晚期成熟。值得注意的是,SHED-CM抑制rankl诱导的ROS生成,而BMSC-CM不抑制。SHED-CM增加了抗氧化酶编码基因的表达。LC-MS分析鉴定了7种在SHED-CM中独特富集的激活内源性抗氧化系统的蛋白质。中和这些蛋白的抗体可以恢复rankl诱导的ROS生成和破骨细胞分化。结论:SHED-CM抑制破骨细胞生成,部分是通过激活破骨细胞前体中的多种抗氧化酶,突出了其治疗骨破坏性疾病的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Factors secreted from the stem cells of human exfoliated deciduous teeth inhibit osteoclastogenesis through the activation of the endogenous antioxidant system

Factors secreted from the stem cells of human exfoliated deciduous teeth inhibit osteoclastogenesis through the activation of the endogenous antioxidant system

Objectives

Systemic administration of conditioned medium (CM) from stem cells derived from human exfoliated deciduous teeth (SHED-CM) in mouse models of rheumatoid arthritis, osteoporosis, and osteoarthritis suppresses excessive osteoclast activity and restores bone integrity. However, the mechanism through which SHED-CM regulates osteoclastogenesis remains largely unknown. In the present study, we examined the anti-osteoclastogenic mechanism of SHED-CM in vitro.

Methods

Bone marrow macrophages and RAW264.7 cells were treated with receptor activator of nuclear factor kappa-Β ligand (RANKL) in the presence of SHED-CM or CM from bone marrow mesenchymal stem cells (BMSC-CM). Osteoclast differentiation was assessed using tartrate-resistant acid phosphatase staining, actin ring formation, and expression of osteoclast-specific markers. RANKL-induced reactive oxygen species (ROS) production was analyzed as a critical mediator of osteoclastogenesis. The activation of endogenous antioxidant gene expression was examined using reverse transcription quantitative PCR. Liquid chromatography with tandem mass spectrometry (LC-MS) was used to identify proteins enriched in SHED-CM, and neutralizing antibodies were used to evaluate their functional roles.

Results

Compared to BMSC-CM, SHED-CM effectively inhibited RANKL-induced early osteoclast differentiation and late maturation. Notably, SHED-CM but not BMSC-CM suppressed RANKL-induced ROS production. SHED-CM increased the expression of genes encoding antioxidant enzymes. The LC-MS analysis identified seven proteins uniquely enriched in SHED-CM that activated the endogenous antioxidant system. Neutralizing antibodies against some of these proteins restore RANKL-induced ROS production and osteoclast differentiation.

Conclusions

SHED-CM inhibited osteoclastogenesis, partially through the activation of multiple antioxidant enzymes in osteoclast precursors, highlighting its potential for treating bone-destructive diseases.
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来源期刊
Journal of Oral Biosciences
Journal of Oral Biosciences DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
4.40
自引率
12.50%
发文量
57
审稿时长
37 days
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