Genes and Diseases (Nov 2021)
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,
- Jian Yang,
- Le Shen,
- Lin Cai,
- Hue H. Luu
Affiliations
- Yukun Mao
- Departments of Spine Surgery and Musculoskeletal Tumor, and Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430072, PR China; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Na Ni
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Ministry of Education Key Laboratory of Diagnostic Medicine, and the School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, PR China
- Linjuan Huang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Departments of Nephrology, and Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
- Jiaming Fan
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Ministry of Education Key Laboratory of Diagnostic Medicine, and the School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, PR China
- Hao Wang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Ministry of Education Key Laboratory of Diagnostic Medicine, and the School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, PR China
- Fang He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Ministry of Education Key Laboratory of Diagnostic Medicine, and the School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, PR China
- Qing Liu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Department of Spine Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410011, PR China
- Deyao Shi
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Department of Orthopaedic Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, PR China
- Kai Fu
- Departments of Spine Surgery and Musculoskeletal Tumor, and Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430072, PR China; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Mikhail Pakvasa
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; 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, Chicago, IL 60637, USA
- William Wagstaff
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Andrew Blake Tucker
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; 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, Chicago, IL 60637, USA
- Connie Chen
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Russell R. Reid
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; 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, Chicago, IL 60637, USA
- Rex C. Haydon
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Sherwin H. Ho
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Michael J. Lee
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
- Tong-Chuan He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; 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, Chicago, IL 60637, USA
- Jian Yang
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
- Le Shen
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; 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, Chicago, IL 60637, USA
- Lin Cai
- Departments of Spine Surgery and Musculoskeletal Tumor, and Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430072, PR China; Corresponding author. Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, 430071, China.
- Hue H. Luu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Corresponding author. Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC3079, Chicago, IL 60637, USA. Fax: +(773) 834 4598.
- Journal volume & issue
-
Vol. 8,
no. 6
pp. 918 – 930
Abstract
As 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.
