Transforming Growth Factor Beta (TGF-β) Regulates Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Promoting Wnt Signaling Pathway in Atrophic Nonunion

被引:0
作者
Zhan, Minqing [1 ]
Wang, Mingming [2 ]
Zhang, Juan [3 ]
Jiang, Xiaorui [4 ]
机构
[1] Weihaiwei Peoples Hosp, Dept Orthopaed, Weihai 264200, Shandong, Peoples R China
[2] Binzhou Peoples Hosp, Dept Trauma & Sports Med, Binzhou 256600, Shandong, Peoples R China
[3] Binzhou Peoples Hosp, Dept Orthopaed, Binzhou 256600, Shandong, Peoples R China
[4] Qingdao Univ, Yantai Yuding Hosp, Dept Orthopaed, Yantai 264000, Shandong, Peoples R China
关键词
TGF-beta; Atrophic Nonunion; Wnt Signaling Pathway; Proliferation; Osteogenic Differentiation;
D O I
10.1166/jbt.2020.2236
中图分类号
Q813 [细胞工程];
学科分类号
摘要
During atrophic nonunion, Wnt signaling pathway is inhibited, resulting in inhibition of BMSC osteogenic differentiation. TGF-beta regulates growth and development of the body. However, TGF-beta's effect on osteogenic differentiation of BMSCs in atrophic nonunion has not been reported. The bone tissue and serum of patients with atrophic nonunion and normal healing fractures were collected, and TGF-beta mRNA and serum secretion were analyzed by Real time PCR and ELISA. Rat BMSCs were cultured and randomly divided into control group, TGF-beta group and TGF-beta siRNA group which was transfected with pcDNA-TGF-beta plasmid or TGF-beta siRNA respectively followed by analysis of cell proliferation by MTT assay, alkaline phosphatase (ALP) activity, Caspase3 activity, expression of RUNX2 and OPN and PPAR gamma 2 mRNA by Real time PCR, and WNT5A and FZD3 expression by Western blot. TGF-beta mRNA level and secretion in patients with atrophic nonunion was significantly reduced compared with patients with normal healing fractures (P < 0.05). Transfection of TGF-beta siRNA down-regulated TGF-beta expression in BMSCs, significantly inhibited cell proliferation, increased Caspase3 activity, decreased ALP activity, RUNX2 and OPN expression, increased PPAR gamma 2 expression and deceased WNT5A and FZD3 expression (P < 0.05). However, transfection of pcDNA-TGF-beta plasmid up-regulated TGF-beta expression in BMSCs and reversed the above changes (P < 0.05). TGF-beta is reduced in atrophic nonunion patients. Targeting TGF-beta promotes BMSCs proliferation and osteogenic differentiation by regulating Wnt signaling pathway.
引用
收藏
页码:265 / 270
页数:6
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