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含Jumonji结构域蛋白1C的沉默通过抑制核因子-κB信号传导抑制骨髓间充质干细胞的成骨分化

Silencing of Jumonji domain-containing 1C inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells nuclear factor-κB signaling.

作者信息

Li Jing-Yi, Wang Ting-Ting, Ma Li, Zhang Yu, Zhu Di

机构信息

Department of Medical Cosmetology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Department of General Gerontology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.

出版信息

World J Stem Cells. 2024 Feb 26;16(2):151-162. doi: 10.4252/wjsc.v16.i2.151.

Abstract

BACKGROUND

Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity. During osteoporosis, bone mesenchymal stem cells (BMSCs) exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts, resulting in bone loss. Jumonji domain-containing 1C () has been demonstrated to suppress osteoclastogenesis.

AIM

To examine the effect of on the osteogenesis of BMSCs and the potential underlying mechanism.

METHODS

BMSCs were isolated from mouse bone marrow tissues. Oil Red O staining, Alizarin red staining, alkaline phosphatase staining and the expression of adipogenic and osteogenic-associated genes were assessed to determine the differentiation of BMSCs. Bone marrow-derived macrophages (BMMs) were incubated with receptor activator of nuclear factor-kappa Β ligand to induce osteoclast differentiation, and osteoclast differentiation was confirmed by tartrate-resistant acid phosphatase staining. Other related genes were measured reverse transcription coupled to the quantitative polymerase chain reaction and western blotting. Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6 and interleukin-1 beta.

RESULTS

The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated. mRNA and protein expression was upregulated in BMSCs after osteoblast induction, while p-nuclear factor-κB (NF-κB) and inflammatory cytokines were not significantly altered. Knockdown of repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs. Moreover, expression decreased during BMM osteoclast differentiation.

CONCLUSION

The /NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.

摘要

背景

骨质疏松症是一种常见的代谢性骨病,由破骨细胞活性与成骨细胞活性失衡所致。在骨质疏松症发生过程中,骨髓间充质干细胞(BMSCs)向脂肪细胞分化的能力增强,向成骨细胞分化的能力减弱,导致骨质流失。含Jumonji结构域1C()已被证明可抑制破骨细胞生成。

目的

研究对BMSCs成骨作用的影响及其潜在机制。

方法

从小鼠骨髓组织中分离BMSCs。通过油红O染色、茜素红染色、碱性磷酸酶染色以及评估脂肪生成和成骨相关基因的表达来确定BMSCs的分化情况。将骨髓来源的巨噬细胞(BMMs)与核因子κB受体活化因子配体孵育以诱导破骨细胞分化,并通过抗酒石酸酸性磷酸酶染色确认破骨细胞分化。通过逆转录耦合定量聚合酶链反应和蛋白质印迹法检测其他相关基因。采用酶联免疫吸附测定法检测炎性细胞因子水平,包括肿瘤坏死因子α、白细胞介素-6和白细胞介素-1β。

结果

评估了从小鼠骨髓样本中分离的BMSCs的成骨和脂肪生成分化潜能。成骨细胞诱导后,BMSCs中的mRNA和蛋白表达上调,而磷酸化核因子κB(NF-κB)和炎性细胞因子无明显变化。敲低可抑制BMSCs的成骨分化,增强NF-κB激活和炎性细胞因子释放。此外,在BMM破骨细胞分化过程中表达降低。

结论

/NF-κB信号通路可能参与BMSCs成骨分化,可能在骨质疏松症发病机制中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eff/10915961/126e45a13ed6/WJSC-16-151-g001.jpg

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