Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway.
HSPA1A, which encodes cognate heat shock protein 70, plays important roles in various cellular metabolic pathways. To investigate its effects on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its expression level was compared between undifferentiated and differentiated BMSCs. Rat HSPA1A overexpression in BMSCs increased osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Moreover, it upregulated β-catenin and downregulated DKK1 and SOST. The enhanced osteogenesis due to HSPA1A overexpression was partly rescued by a Wnt/β-catenin inhibitor. Additionally, using a rat tibial fracture model, a sheet of HSPA1A-overexpressing BMSCs improved bone fracture healing, as determined by imaging and histological analysis. Taken together, these findings suggest that HSPA1A overexpression enhances osteogenic differentiation of BMSCs, partly through Wnt/β-catenin.
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Wei
W
Zhang
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Deting
D
Xue
Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Houfa
H
Yin
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Shengdong
S
Wang
Department of Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, 310009, Hangzhou, Zhejiang Province, China.
Chao
C
Li
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Erman
E
Chen
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Dongcai
D
Hu
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Yiqing
Y
Tao
Department of Orthopedics, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang Province, China.
Jiawei
J
Yu
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Qiang
Q
Zheng
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Xiang
X
Gao
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Zhijun
Z
Pan
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D017102:Fracture Healing; D005819:Genetic Markers / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; C531384:Dkk1 protein, rat; D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins; C097210:Hspa1a protein, rat; D036341:Intercellular Signaling Peptides and Proteins; C486031:Sost protein, rat; D051176:beta Catenin