Increased BMPR1A Expression Enhances the Adipogenic Differentiation of Mesenchymal Stem Cells in Patients with Ankylosing Spondylitis

被引:12
作者
Liu, Zhenhua [1 ,2 ]
Wang, Peng [1 ]
Cen, Shuizhong [3 ]
Gao, Liangbin [3 ]
Xie, Zhongyu [1 ]
Wu, Xiaohua [4 ]
Su, Hongjun [4 ]
Wu, Yanfeng [4 ]
Shen, Huiyong [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Orthoped, 3025 Sherman Rd Middle, Shenzhen 518033, Guangdong, Peoples R China
[2] Southern Med Univ, Zhujiang Hosp, Dept Orthoped, 253 Ind Ave Middle, Guangzhou 510128, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Orthoped, 107 Yan Jiang Rd West, Guangzhou 510120, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Ctr Biotherapy, 107 Yan Jiang Rd West, Guangzhou 510120, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
BONE MORPHOGENETIC PROTEIN-2; RESONANCE-IMAGING PREDICT; ADIPOCYTE DIFFERENTIATION; OSTEOGENIC DIFFERENTIATION; ADIPOSE-TISSUE; OSTEOBLAST DIFFERENTIATION; PRECURSOR CELLS; FAT; PROMOTES; MRI;
D O I
10.1155/2019/4143167
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Objective. To investigate the adipogenic differentiation capacity of mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients and explore the mechanism of abnormal MSC adipogenesis in AS. Methods. MSCs from patients with AS (ASMSCs) and healthy donors (HDMSCs) were cultured in adipogenic differentiation medium for up to 21 days. Adipogenic differentiation was determined using oil red O (ORO) staining and quantification and was confirmed by assessing adipogenic marker expression (PPAR-gamma, FABP4, and adiponectin). Gene expression of adipogenic markers was detected using qRT-PCR. Protein levels of adipogenic markers and signaling pathway-related molecules were assessed via Western blotting. Levels of bone morphogenetic proteins 4, 6, 7, and 9 were determined using enzyme-linked immunosorbent assays. Lentiviruses encoding short hairpin RNAs (shRNAs) were constructed to reverse abnormal bone morphogenetic protein receptor 1A (BMPR1A) expression and evaluate its role in abnormal ASMSC adipogenic differentiation. Bone marrow fat content was assessed using hematoxylin and eosin (HE) staining. BMPR1A expression in bone marrow MSCs was measured using immunofluorescence staining. Results. ASMSCs exhibited a greater adipogenic differentiation capacity than HDMSCs. During adipogenesis, ASMSCs expressed BMPR1A at higher levels, which activated the BMP-pSmad1/5/8 signaling pathway and increased adipogenesis. BMPR1A silencing using an shRNA eliminated the difference in adipogenic differentiation between HDMSCs and ASMSCs. Moreover, HE and immunofluorescence staining showed higher bone marrow fat content and BMPR1A expression in patients with AS than in healthy donors. Conclusion. Increased BMPR1A expression induces abnormal ASMSC adipogenic differentiation, potentially contributing to fat metaplasia and thus new bone formation in patients with AS.
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页数:13
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