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微小RNA-705调控小鼠下颌骨骨髓间充质干细胞的分化。

MicroRNA-705 regulates the differentiation of mouse mandible bone marrow mesenchymal stem cells.

作者信息

Yang Xiao Hong, Yang Kun, An Yu Lin, Wang Li Bo, Luo Guo, Hu Xiao Hua

机构信息

Department of Prosthetics, the Affiliated Stomatology Hospital of Zunyi Medical University, Zunyi Medical University, Zunyi, Guizhou, China.

Department of Periodontology, the Affiliated Stomatology Hospital of Zunyi Medical University, Zunyi Medical university, Zunyi, Guizhou, China.

出版信息

PeerJ. 2019 Jan 10;7:e6279. doi: 10.7717/peerj.6279. eCollection 2019.

Abstract

The craniofacial skeleton is the foundation of most stomatological treatments, including prosthodontics and maxillofacial surgery. Although histologically similar to the appendicular skeleton, the craniofacial skeleton manifests many unique properties in response to external stimuli and signals. However, the mandibular or maxillary bone marrow mesenchyme, which is the intrinsic foundation of the functions of craniofacial skeleton, has not been well studied, and its homeostasis mechanism remains elusive. Osteoporosis is a systemic disease that affects all skeletons and is characterized by bone mass loss. Osteoporotic bone marrow mesenchymal stem cells (BMMSCs) exhibit disturbed homeostasis and distorted lineage commitment. Many reports have shown that microRNAs (miRNAs) play important roles in regulating MSCs homeostasis. Here, to obtain a better understanding of mandibular bone marrow MSCs homeostasis, we isolated and cultured mandible marrow MSCs from mouse mandibles. Using miR-705 mimics and an inhibitor, we demonstrated that miR-705 played a vital role in shifting the mandibular MSCs lineage commitment . Utilizing an osteoporosis mouse model, we demonstrated that MSCs from ovariectomized (OVX) mouse mandibular bone marrow exhibited impaired osteogenic and excessive adipogenic differentiation. miR-705 was found overexpressed in OVX mandibular MSCs. The knock down of miR-705 partially attenuated the differentiation disorder of the OVX mandibular MSCs by upregulating the expression of osteogenic marker genes but suppressing adipogenic genes. Taken together, our findings provide a better understanding of the homeostasis mechanism of mandibular BMMSCs and a novel potential therapeutic target for treating mandibular osteoporosis.

摘要

颅面骨骼是包括口腔修复学和颌面外科在内的大多数口腔治疗的基础。虽然在组织学上与附属骨骼相似,但颅面骨骼在对外界刺激和信号的反应中表现出许多独特的特性。然而,作为颅面骨骼功能的内在基础的下颌或上颌骨髓间充质,尚未得到充分研究,其稳态机制仍然难以捉摸。骨质疏松症是一种影响所有骨骼的全身性疾病,其特征是骨量减少。骨质疏松性骨髓间充质干细胞(BMMSCs)表现出稳态紊乱和谱系定向异常。许多报告表明,微小RNA(miRNAs)在调节间充质干细胞稳态中起重要作用。在这里,为了更好地了解下颌骨髓间充质干细胞的稳态,我们从小鼠下颌骨中分离并培养了下颌骨髓间充质干细胞。使用miR-705模拟物和抑制剂,我们证明miR-705在改变下颌间充质干细胞谱系定向中起关键作用。利用骨质疏松小鼠模型,我们证明来自去卵巢(OVX)小鼠下颌骨髓的间充质干细胞表现出成骨受损和脂肪生成过度分化。发现miR-705在OVX下颌间充质干细胞中过表达。敲低miR-705通过上调成骨标记基因的表达但抑制脂肪生成基因,部分减轻了OVX下颌间充质干细胞的分化障碍。综上所述,我们的研究结果为更好地理解下颌BMMSCs的稳态机制以及治疗下颌骨质疏松症提供了一个新的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1c/6330203/02d7217ef7c7/peerj-07-6279-g001.jpg

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