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urn:hdl:2445/177363 MicroRNA-322 (miR-322) and its target protein Tob2 modulate Osterix (Osx) mRNA stability Gamez Molina, Beatriz Rodríguez Carballo, Edgardo Bartrons Bach, Ramon Rosa López, José Luis Ventura Pujol, Francesc Cicle cel·lular Expressió gènica Citologia Factors de transcripció Cell cycle Gene expression Cytology Transcription factors Osteogenesis depends on a coordinated network of signals and transcription factors such as Runx2 and Osterix. Recent evidence indicates that microRNAs (miRNAs) act as important post-transcriptional regulators in a large number of processes, including osteoblast differentiation. In this study, we performed miRNA expression profiling and identified miR-322, a BMP-2-down-regulated miRNA, as a regulator of osteoblast differentiation. We report miR-322 gain- and loss-of-function experiments in C2C12 and MC3T3-E1 cells and primary cultures of murine bone marrow-derived mesenchymal stem cells. We demonstrate that overexpression of miR-322 enhances BMP-2 response, increasing the expression of Osx and other osteogenic genes. Furthermore, we identify Tob2 as a target of miR-322, and we characterize the specific Tob2 3′-UTR sequence bound by miR-322 by reporter assays. We demonstrate that Tob2 is a negative regulator of osteogenesis that binds and mediates degradation of Osx mRNA. Our results demonstrate a new molecular mechanism controlling osteogenesis through the specific miR-322/Tob2 regulation of specific target mRNAs. This regulatory circuit provides a clear example of a complex miRNA-transcription factor network for fine-tuning the osteoblast differentiation program. 2021-05-18T11:51:57Z 2021-05-18T11:51:57Z 2013-05-17 2021-05-18T11:51:57Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1074/jbc.M112.432104 Journal of Biological Chemistry, 2013, vol. 288, num. 20, p. 14264-14275 https://doi.org/10.1074/jbc.M112.432104 (c) American Society for Biochemistry and Molecular Biology, 2013 info:eu-repo/semantics/openAccess American Society for Biochemistry and Molecular Biology Articles publicats en revistes (Ciències Fisiològiques)