MicroRNAs and post-transcriptional regulation of skeletal development

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   Figure 1

   Biogenesis and function of miRNAs. miRNAs are transcribed as long primary transcripts (pri-miRNAs) in the nucleus and are later recognized by Drosha and its cofactor DGCR8 to generate a pre-miRNA. Pre-miRNAs reach the cytoplasm through exportin 5 and are processed by Dicer into a mature miRNA–miRNA* duplex. RNA-induced silencing complex (RISC) recruits the selected miRNA strand and targets the miRNA–RISC complex to the specific 3′-UTR mRNA, while the miRNA* strand is degraded. Depending on the miRNA–mRNA complementarity, miRNA degrades the target mRNA or inhibits its translation. AGO2, argonaute 2.
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   Figure 2

   Schematic summary of miRNA role in osteoblast and chondroblast differentiation. A cohort of transcription factors tightly regulates osteoblast and chondroblast commitment from osteochondroprogenitors during skeletal development. miRNAs are important players during this commitment regulating the expression of these transcription factors, therefore allowing or blocking the differentiation process.
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   Figure 3

   Effects of miRNAs on osteoclast differentiation. miRNAs affect different molecules related to osteoclast commitment such as RANK or M-CSF receptor, among others. miRNA expression leads to changes in osteoclast activity in vitro and also to alterations in bone resorption in vivo. OPG, osteopontegrin.
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   Figure 4

   Interplay between the BMP pathway and miRNAs. miRNAs act at different steps of BMP signaling: from those involving BMP receptors to those involving SMADs.
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   Figure 5

   miRNAs involved in the Wnt/β-catenin pathway. miRNAs target several molecules of the Wnt/β-catenin pathway: LRP co-receptors, proteins of the β-catenin degradation complex, or several inhibitory molecules such as DKK or SOST.

• © 2014 Society for Endocrinology