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已发表论文
微小 RNA-874-3p 可能是原发性甲状旁腺功能亢进症所致骨质疏松症的一个潜在促成因素
Authors Cheng K, Bai R, Li M, Wei Y, Li Z, Zhao X, Cao R, Wang Z, Tan S, Zha Y, Jiang X , Lu S
Received 2 June 2025
Accepted for publication 4 October 2025
Published 18 November 2025 Volume 2025:20 Pages 2079—2089
DOI https://doi.org/10.2147/CIA.S538129
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Zhi-Ying Wu
Kaiyuan Cheng,1,* Ruifeng Bai,2,* Minjuan Li,1 Yongjie Wei,3 Zhigang Li,3 Xian Zhao,4 Renwei Cao,4 Zhongyu Wang,4 Shen Tan,5 Yejun Zha,1 Xieyuan Jiang,1,6 Shuai Lu1,6
1Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, People’s Republic of China; 4Department of Orthopedics Trauma, Beijing Jishuitan Hospital, Peking University Fourth School, Beijing, People’s Republic of China; 5Department of General Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Beijing Research Institute of Traumatology and Orthopaedics, Beijing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Shuai Lu, Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email jst_doctorlu@163.com Xieyuan Jiang, Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email jxytrauma@163.com
Background: Dysregulation of microRNAs contributes to bone diseases. However, the microRNAs involved in primary hyperparathyroidism (PHPT)-induced osteoporosis remain unknown.
Methods: The parathyroid tissue samples were obtained from PHPT patients with or without osteoporosis (n = 5/group) during parathyroid resection and subjected to high throughput microRNA sequencing. The differentially expressed microRNAs were identified and further verified using qRT-PCR. Alizarin Red Staining was performed to detected the osteogenic differentiation. Gain- and loss-of-function assays were performed to investigate the role of miR-874-3p, which was upregulated in PHPT patients with osteoporosis, in human mesenchymal stem cells (hMSCs) undergoing osteoblastic differentiation.
Results: We identified 32 significantly upregulated and 18 significantly downregulated microRNAs in PHPT patients with osteoporosis. miR-874-3p was increased in PHPT osteoporosis patients, meanwhile, miR-874-3p in parathyroid tissue and peripheral blood extracellular vesicles of PHPT osteoporosis mice were increased. The miR-874-3p level was remarkably elevated in hMSCs grown in osteogenic medium. Overexpression of miR-874-3p repressed the hMSC osteogenic differentiation and reduced the osteogenic marker expression in hMSCs, whereas miR-874-3p inhibitor showed a contrasting effect. The results of the dual luciferase reporting system showed that miR-874-3p could reduce the luciferase activity of wild-type FTO-WT-3 ‘-UTR. However, there was no significant change in the luciferase activity of the mutant compared with the control group.
Conclusion: MiR-874-3p might specifically binds to FTO suppress osteogenic differentiation of hMSCs, thereby contributing to the development of osteoporosis in PHPT patients.
Keywords: microRNAs, primary hyperparathyroidism, osteoporosis, next-generation sequencing, mesenchymal stem cells
1Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, People’s Republic of China; 4Department of Orthopedics Trauma, Beijing Jishuitan Hospital, Peking University Fourth School, Beijing, People’s Republic of China; 5Department of General Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Beijing Research Institute of Traumatology and Orthopaedics, Beijing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Shuai Lu, Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email jst_doctorlu@163.com Xieyuan Jiang, Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email jxytrauma@163.com
Background: Dysregulation of microRNAs contributes to bone diseases. However, the microRNAs involved in primary hyperparathyroidism (PHPT)-induced osteoporosis remain unknown.
Methods: The parathyroid tissue samples were obtained from PHPT patients with or without osteoporosis (n = 5/group) during parathyroid resection and subjected to high throughput microRNA sequencing. The differentially expressed microRNAs were identified and further verified using qRT-PCR. Alizarin Red Staining was performed to detected the osteogenic differentiation. Gain- and loss-of-function assays were performed to investigate the role of miR-874-3p, which was upregulated in PHPT patients with osteoporosis, in human mesenchymal stem cells (hMSCs) undergoing osteoblastic differentiation.
Results: We identified 32 significantly upregulated and 18 significantly downregulated microRNAs in PHPT patients with osteoporosis. miR-874-3p was increased in PHPT osteoporosis patients, meanwhile, miR-874-3p in parathyroid tissue and peripheral blood extracellular vesicles of PHPT osteoporosis mice were increased. The miR-874-3p level was remarkably elevated in hMSCs grown in osteogenic medium. Overexpression of miR-874-3p repressed the hMSC osteogenic differentiation and reduced the osteogenic marker expression in hMSCs, whereas miR-874-3p inhibitor showed a contrasting effect. The results of the dual luciferase reporting system showed that miR-874-3p could reduce the luciferase activity of wild-type FTO-WT-3 ‘-UTR. However, there was no significant change in the luciferase activity of the mutant compared with the control group.
Conclusion: MiR-874-3p might specifically binds to FTO suppress osteogenic differentiation of hMSCs, thereby contributing to the development of osteoporosis in PHPT patients.
Keywords: microRNAs, primary hyperparathyroidism, osteoporosis, next-generation sequencing, mesenchymal stem cells