
miR-199a/b-5p act as pro-chondrogenic regulators by downregulating the expression of FZD6, ITGA3 and CAV1, thereby promoting chondrocyte differentiation and cartilage formation.


coremsg

Changes in chondrocyte gene expression can contribute to the development of osteoarthritis (OA), and so recognition of the regulative processes during chondrogenesis can lead to a better understanding of OA. microRNAs (miRNAs) are key regulators of gene expression in chondrocytes/OA and we have used a combined experimental, bioinformatic, and systems biology approach to explore the multiple miRNA-mRNA interactions that regulate chondrogenesis. A longitudinal chondrogenesis bioinformatic analysis identified paralogues miR-199a-5p and miR-199b-5p as pro-chondrogenic regulators. Experimental work demonstrated alteration of miR-199a-5p or miR-199b-5p expression led to significant inverse modulation of key chondrogenic genes and extracellular matrix production. miR-199a/b-5p targets FZD6, ITGA3 and CAV1 were identified by inhibition experiments and verified as direct targets by luciferase assay. The experimental work was used to generate and parameterize a multi-miRNA 14-day chondrogenesis kinetic model to be used as a repository for the experimental work and as a resource for further investigation of this system. This is the first multi-miRNA model of a chondrogenesis-based system, and highlights the complex relationships between regulatory miRNAs, and their target mRNAs.

### Competing Interest Statement

The authors have declared no competing interest.

Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis

bioinformatic-and-experimental-analysis-reveals-mir-199a-b-5p-as-key-regulators-of-chondrogenesis


Bioinformatic and Experimental Analysis Reveals miR-199a/b-5p as Key Regulators of Chondrogenesis
