Zhongyu Xie1, Jinteng Li1, Peng Wang1, Yuxi Li1, Xiaohua Wu1, Shan Wang1, Hongjun Su1, Wen Deng1, Zhenhua Liu1, Shuizhong Cen1, Yi Ouyang1, Yanfeng Wu1, Huiyong Shen2. 1. From the Department of Orthopedics, and the Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P.R. China.Z. Xie, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; J. Li, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; P. Wang, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Y. Li, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; X. Wu, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; S. Wang, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; H. Su, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; W. Deng, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Z. Liu, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; S. Cen, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Y. Ouyang, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Y. Wu, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; H. Shen, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. 2. From the Department of Orthopedics, and the Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P.R. China.Z. Xie, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; J. Li, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; P. Wang, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Y. Li, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; X. Wu, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; S. Wang, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; H. Su, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; W. Deng, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Z. Liu, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; S. Cen, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Y. Ouyang, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Y. Wu, MD, Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; H. Shen, MD, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. shenhuiy@yeah.net wuyanfengcn@126.com.
Abstract
OBJECTIVE: We previously demonstrated that mesenchymal stem cells (MSC) from patients with ankylosing spondylitis (AS; ASMSC) have a greater osteogenic differentiation capacity than MSC from healthy donors (HDMSC) and that this difference underlies the pathogenesis of pathological osteogenesis in AS. Here we compared expression levels of long noncoding RNA (lncRNA) and mRNA between osteogenically differentiated ASMSC and HDMSC and explored the precise mechanism underlying abnormal osteogenic differentiation in ASMSC. METHODS: HDMSC and ASMSC were induced with osteogenic differentiation medium for 10 days. Microarray analyses were then performed to identify lncRNA and mRNA differentially expressed between HDMSC and ASMSC, which were then subjected to bioinformatics analysis and confirmed by quantitative real-time PCR (qRT-PCR) assays. In addition, coding-non-coding gene co-expression (CNC) networks were constructed to examine the relationships between the lncRNA and mRNA expression patterns. RESULTS: A total of 520 lncRNA and 665 mRNA were differentially expressed in osteogenically differentiated ASMSC compared with HDMSC. Bioinformatics analysis revealed 64 signaling pathways with significant differences, including transforming growth factor-β signaling. qRT-PCR assays confirmed the reliability of the microarray data. The CNC network indicated that 4 differentially expressed lncRNA, including lnc-ZNF354A-1, lnc-LIN54-1, lnc-FRG2C-3, and lnc-USP50-2 may be involved in the abnormal osteogenic differentiation of ASMSC. CONCLUSION: Our study characterized the differential lncRNA and mRNA expression profiles of osteogenically differentiated ASMSC and identified 4 lncRNA that may participate in the abnormal osteogenic differentiation of ASMSC. These results provide insight into the pathogenesis of pathological osteogenesis in AS.
OBJECTIVE: We previously demonstrated that mesenchymal stem cells (MSC) from patients with ankylosing spondylitis (AS; ASMSC) have a greater osteogenic differentiation capacity than MSC from healthy donors (HDMSC) and that this difference underlies the pathogenesis of pathological osteogenesis in AS. Here we compared expression levels of long noncoding RNA (lncRNA) and mRNA between osteogenically differentiated ASMSC and HDMSC and explored the precise mechanism underlying abnormal osteogenic differentiation in ASMSC. METHODS: HDMSC and ASMSC were induced with osteogenic differentiation medium for 10 days. Microarray analyses were then performed to identify lncRNA and mRNA differentially expressed between HDMSC and ASMSC, which were then subjected to bioinformatics analysis and confirmed by quantitative real-time PCR (qRT-PCR) assays. In addition, coding-non-coding gene co-expression (CNC) networks were constructed to examine the relationships between the lncRNA and mRNA expression patterns. RESULTS: A total of 520 lncRNA and 665 mRNA were differentially expressed in osteogenically differentiated ASMSC compared with HDMSC. Bioinformatics analysis revealed 64 signaling pathways with significant differences, including transforming growth factor-β signaling. qRT-PCR assays confirmed the reliability of the microarray data. The CNC network indicated that 4 differentially expressed lncRNA, including lnc-ZNF354A-1, lnc-LIN54-1, lnc-FRG2C-3, and lnc-USP50-2 may be involved in the abnormal osteogenic differentiation of ASMSC. CONCLUSION: Our study characterized the differential lncRNA and mRNA expression profiles of osteogenically differentiated ASMSC and identified 4 lncRNA that may participate in the abnormal osteogenic differentiation of ASMSC. These results provide insight into the pathogenesis of pathological osteogenesis in AS.