caa a22 4500 60623456X CHVBK 20210128101238.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2404-4 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2404-4 MiR-21 overexpression improves osteoporosis by targeting RECK [Elektronische Daten] [Weigong Zhao, Yanying Dong, Caijun Wu, Yunfeng Ma, Yaofeng Jin, Yanhong Ji] Osteoporosis is a kind of metabolic bonedisorder. MicroRNA-21 (miR-21) has been proven to play an important role in bone formation, whereas its role in osteoporosis is unclear. In the present study, miR-21 expression was inhibited by TNF-α in mesenchymal stem cells (MSCs). TNF-α induced cell apoptosis, and inhibited cell proliferation and differentiation of MSCs. Whereas the effect was reversed by miR-21 mimics. Expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) which is a predicted target of miR-21 was inhibited by miR-21 mimics. A luciferase reporter gene assay showed that miR-21 directly bound to RECK 3′-UTR. The effect of TNF-α on MSCs was reversed by RECK siRNA which was consistent with miR-21 mimics. The expression of MT1-MMP was inhibited by TNF-α and enhanced by RECK siRNA and miR-21 mimics. For the in vivo study, an osteoporosis model (OVX) was established by bilateral oophorectomy in mice. The expression of miR-21 decreased and RECK increased in the OVX mice. When treated with lentiviral RECK shRNA, the osteocalcin concentration and alkaline phosphate activity of the OVX mice decreased. The bone mineral density of the right femur mid-diaphysis was improved by RECK shRNA. Collectively, miR-21 modulated the osteoporosis by targeting RECK. These results emphasize the role of miR-21 during osteoporosis and suggest RECK might be a new medical target for osteoporosis. Springer Science+Business Media New York, 2015 Osteoporosis nationallicence miR-21 nationallicence RECK nationallicence MT1-MMP nationallicence MSCs : Mesenchymal stem cells nationallicence RECK : Reversion-inducing cysteine-rich protein with Kazal motifs nationallicence OVX : Ovariectomy nationallicence MMP : Matrix metalloproteinase nationallicence ALP : Alkaline phosphate nationallicence BMD : Bone mineral density nationallicence Zhao Weigong Department of Orthopedics, The 1st Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Street, 710061, Xi'an, Shaanxi, China aut Dong Yanying Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut Wu Caijun Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut Ma Yunfeng Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut Jin Yaofeng Department of Pathology, The 2nd Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710004, Xi'an, Shaanxi, China aut Ji Yanhong Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 125-133 0300-8177 405:1-2<125 2015 405 11010 https://doi.org/10.1007/s11010-015-2404-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2404-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhao Weigong Department of Orthopedics, The 1st Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Street, 710061, Xi'an, Shaanxi, China aut NATIONALLICENCE 700 1- Dong Yanying Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut NATIONALLICENCE 700 1- Wu Caijun Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut NATIONALLICENCE 700 1- Ma Yunfeng Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut NATIONALLICENCE 700 1- Jin Yaofeng Department of Pathology, The 2nd Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710004, Xi'an, Shaanxi, China aut NATIONALLICENCE 700 1- Ji Yanhong Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Street, 710061, Xi'an, Shaanxi, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 125-133 0300-8177 405:1-2<125 2015 405 11010