Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs)

Yukun Mao; Na Ni; Linjuan Huang; Jiaming Fan; Hao Wang; Fang He; Qing Liu; Deyao Shi; Kai Fu; Mikhail Pakvasa; William Wagstaff; Andrew Blake Tucker; Connie Chen; Russell R. Reid; Rex C. Haydon; Sherwin H. Ho; Michael J. Lee; Tong-Chuan He; Hue H. Luu

doi:10.1016/j.gendis.2021.04.004

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Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs)

更新时间：2022-06-24

- Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs)
- Genes & Diseases Vol. 8, Issue 6, (2021)
- 作者机构：
  
  1. Departments of Spine Surgery and Musculoskeletal Tumor, and Neurosurgery, Zhongnan Hospital of Wuhan University,Hubei Province,Wuhan,PR China,430072
  2. Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center,IL,Chicago,USA,60637
  3. Ministry of Education Key Laboratory of Diagnostic Medicine, and the School of Laboratory Medicine, Chongqing Medical University,Chongqing,PR China,400016
  4. Departments of Nephrology, and Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University,Chongqing,PR China,400016
  5. Department of Spine Surgery, Second Xiangya Hospital, Central South University,Hunan Province,Changsha,PR China,410011
  6. Department of Orthopaedic Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology,Hubei Province,Wuhan,PR China,430022
  7. Section of Plastic Surgery and Laboratory of Craniofacial Biology and Development, and Section of Surgical Research, Department of Surgery, The University of Chicago Medical Center,IL,Chicago,USA,60637
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.04.004
  CLC：
- Published：2021，
  
  Published Online：1 November 2021，
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Yukun Mao, Na Ni, Linjuan Huang, et al. Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs). [J]. Genes & Diseases 8(6).(2021)
DOI：

Yukun Mao, Na Ni, Linjuan Huang, et al. Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs). [J]. Genes & Diseases 8(6).(2021) DOI： 10.1016/j.gendis.2021.04.004.

摘要

Abstract

multipotent progenitor cells

mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic

chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs. However

the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood. Emerging evidence indicates that noncoding RNAs

especially microRNAs

may play important roles in regulating MSC differentiation and bone formation. As highly conserved RNA binding proteins

Argonaute (AGO) proteins are essential components of the multi-protein RNA-induced silencing complexes (RISCs)

which are critical for small RNA biogenesis. Here

we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs. We first found that BMP9 up-regulated the expression of

Ago1

Ago2

and

Ago3

in MSCs. By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual

Ago

genes or all four

Ago

genes

we found that silencing individual

Ago

expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs. Furthermore

we demonstrated that simultaneously silencing all four

Ago

genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization

and ectopic bone formation. Collectively

our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

关键词

Keywords

Argonaute (AGO) proteinsBMP9Bone formationLineage-specific differentiationmesenchymal stem cellsmiRNA biogenesisOsteogenic signaling

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