Increased hippocampal excitability in miR-324-null mice
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ABSTRACT:
PROVIDER: PRJNA664937 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12691900.fastq.gz | Fastqsanger.gz | |||
| SRR12691901.fastq.gz | Fastqsanger.gz | |||
| SRR12691902.fastq.gz | Fastqsanger.gz | |||
| SRR12691903.fastq.gz | Fastqsanger.gz | |||
| SRR12691904.fastq.gz | Fastqsanger.gz |
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Project description: microRNAs are non-coding RNAs which modulate the expression of other RNA molecules. One microRNA can target many transcripts, allowing each microRNA to play key roles in many biological pathways. miR-324 is a microRNA previously implicated in bone and cartilage maintenance, defects of which result in common age-related diseases, such as osteoporosis or osteoarthritis (OA). Cartilage damage was increased in both surgically and ageing-induced OA however changes in the cartilage transcriptome were minimal, with few miR-324 predicted targets dysregulated. However, in vivo micro-computed tomography and histology demonstrated that global miR-324-null mice had an increase in bone mineral density, trabecular thickness and cortical thickness, with many parameters increasing with age. The bones of the miR-null mice also had decreased osteocytes numbers and lipid droplets. In vivo TRAP staining revealed a decrease in osteoclasts with histomorphometry demonstrating an increased rate of bone formation in miR-324-null mice. Ex vivo assays revealed that the high bone mass phenotype of the miR-324-null mice resulted from increased osteoblast activity and decreased osteoclastogenesis. RNA-seq and qRT-PCR followed by miR-324 target prediction and validation in osteoblasts, bone marrow macrophages and osteocytes, revealed that the osteoclast fusion regulator Pin1 was a miR-324 target in the osteoclast lineage, Hoxa9 and Samd5 were osteocyte target genes and the master osteogenic regulator Runx2 was a target of miR-324-5p in osteoblasts, the in vitro overexpression of which recapitulated the increased osteogenesis and decreased adipogenesis phenotype observed in vivo. These data point to important roles of miR-324 in skeletal biology. Elucidation of pathways regulated by miR-324 offers promise for the treatment of bone diseases such as osteoporosis.
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