Upregulation of Parkin Accelerates Osteoblastic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells and Bone Regeneration by Enhancing Autophagy and β-Catenin Signaling

Wei Zhang; Wei Zhang; Weiduo Hou; Weiduo Hou; Mo Chen; Erman Chen; Erman Chen; Deting Xue; Deting Xue; Chenyi Ye; Chenyi Ye; Weixu Li; Weixu Li; Zhijun Pan; Zhijun Pan

doi:10.3389/fcell.2020.576104

Frontiers in Cell and Developmental Biology (Sep 2020)

Upregulation of Parkin Accelerates Osteoblastic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells and Bone Regeneration by Enhancing Autophagy and β-Catenin Signaling

Wei Zhang,
Wei Zhang,
Weiduo Hou,
Weiduo Hou,
Mo Chen,
Erman Chen,
Erman Chen,
Deting Xue,
Deting Xue,
Chenyi Ye,
Chenyi Ye,
Weixu Li,
Weixu Li,
Zhijun Pan,
Zhijun Pan

Affiliations

Wei Zhang: Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Wei Zhang: Orthopaedics Research Institute, Zhejiang University, Hangzhou, China
Weiduo Hou: Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Weiduo Hou: Orthopaedics Research Institute, Zhejiang University, Hangzhou, China
Mo Chen: Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China
Erman Chen: Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Erman Chen: Orthopaedics Research Institute, Zhejiang University, Hangzhou, China
Deting Xue: Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Deting Xue: Orthopaedics Research Institute, Zhejiang University, Hangzhou, China
Chenyi Ye: Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Chenyi Ye: Orthopaedics Research Institute, Zhejiang University, Hangzhou, China
Weixu Li: Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Weixu Li: Orthopaedics Research Institute, Zhejiang University, Hangzhou, China
Zhijun Pan: Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Zhijun Pan: Orthopaedics Research Institute, Zhejiang University, Hangzhou, China

DOI: https://doi.org/10.3389/fcell.2020.576104
Journal volume & issue: Vol. 8

Abstract

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Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) plays a key role in bone formation. Parkin, an E3 ubiquitin ligase, related to Parkinson’s disease and aging. Previous studies have indicated that Parkinson’s disease have a higher risk of osteoporotic fracture. To investigate the effects and underlying mechanism of Parkin in the osteogenic differentiation of BMSCs, osteogenic differentiation was analyzed following upregulation or downregulation of Parkin. We found that Parkin was increased during differentiation. Parkin overexpression enhanced osteo-specific markers, and downregulation of Parkin mitigated osteo-specific markers. Moreover, upregulation of Parkin promoted β-catenin expression and autophagy and vice versa. The upregulation of β-catenin enhanced autophagy, and the activation of autophagy also increased the expression of β-catenin in Parkin-downregulated BMSCs. Parkin-overexpressed cell sheets accelerated bone healing in a tibial fracture model. Based on these results, we concluded that Parkin meditates osteoblastic differentiation of BMSCs via β-catenin and autophagy signaling.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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