title: MiR-29a is an enhancer of mineral deposition in bone-derived systems.
abstract: MicroRNAs (miRNAs) provide a mechanism for fine-tuning of intricate cellular processes through post-transcriptional regulation. Emerging evidences indicate that miRNAs play key roles in regulation of osteogenesis. The miR-29 family was previously implicated in mammalian osteoblast differentiation by targeting extracellular matrix molecules and modulating Wnt signaling. Nevertheless, the function of miR-29 in bone formation and homeostasis is not completely understood. Here, we provide novel insights into the biological effect of miR-29a overexpression in a mineralogenic cell system (ABSa15). MiR-29a gain-of-function resulted in significant increase of extracellular matrix mineralization, probably due to accelerated differentiation. We also demonstrated for the first time that miR-29a induced β-catenin protein levels, implying a stimulation of canonical Wnt signaling. Our data also suggests that SPARC is a conserved target of miR-29a, and may contribute to the phenotype observed in ABSa15 cells. Finally, we provide evidences for miR-29a conservation throughout evolution based on sequence homology, synteny analysis and expression patterns. Concluding, miR-29a is a key player in osteogenic differentiation, leading to increased mineralization in vitro, and this function seems to be conserved throughout vertebrate evolution by interaction with canonical Wnt signaling and conservation of targets.
authors.affiliation: Centre of Marine Sciences, University of Algarve, Faro, Portugal; PhD Program in Biomedical Sciences, DCBM, University of Algarve, Portugal. Electronic address: vroberto@ualg.pt.
authors.forename: V P
authors.initials: VP
authors.lastname: Roberto
authors.affiliation: Centre of Marine Sciences, University of Algarve, Faro, Portugal. Electronic address: dtiago@ualg.pt.
authors.forename: D M
authors.initials: DM
authors.lastname: Tiago
authors.affiliation: Centre of Marine Sciences, University of Algarve, Faro, Portugal; PhD Program in Biomedical Sciences, DCBM, University of Algarve, Portugal. Electronic address: irissepol@gmail.com.
authors.forename: I A L
authors.initials: IA
authors.lastname: Silva
authors.affiliation: Centre of Marine Sciences, University of Algarve, Faro, Portugal; Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal. Electronic address: lcancela@ualg.pt.
authors.forename: M L
authors.initials: ML
authors.lastname: Cancela
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D002460:Cell Line; D019143:Evolution, Molecular; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D029941:Fish Proteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015676:Osteonectin / Q000096:biosynthesis* / Q000235:genetics; D021541:Sea Bream / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D029941:Fish Proteins; D035683:MicroRNAs; D015676:Osteonectin
keywords: Conservation; Extracellular matrix mineralization; MiR-29; SPARC; β-Catenin