BoneKEy Reports | BoneKEy Watch

MicroRNA-455 important in chondrogenesis



DOI:10.1038/bonekey.2012.165

Using the in vitro ATDC5 model of chondrogenesis, Swingler et al. investigated the expression of 39 microRNAs (miRNAs or miRs) that are coexpressed with miRNA140. This microRNA has already been identified as being important in osteoarthritis (OA) and cartilage homeostasis. The authors' focus was miR-455, which codes for a cartilage collagen. This was found to be expressed at higher levels in human cartilage from patients with OA than from healthy controls, as was miR-140.

The authors had previously demonstrated that miR-140 can regulate the expression of Smad3 and can control transforming growth factor β (TGFβ)-induced signaling, which is important for maintaining healthy articular cartilage. Here they showed that miR-455 expression was induced by TGFβ1 and TGFβ3 in mouse and human cells. MiRNA-455 also had an inhibitory effect on Smad-dependent signaling, suggesting it has a similarly important role in cartilage homeostasis.

Using the miRNA body map, SMAD2, CHRDL1 and ACVR2B were predicted to be targets for miR-455, through which it can influence TGFβ-induced signaling. The authors propose a link between miRNA140, miRNA-455 and the Smad signaling pathway that could be involved in the development of OA.

Editor's comment: Many miRNAs that are coexpressed with miRNA-140 have been found to be involved in cartilage homeostasis and OA, as well as femoral neck fractures. This study also highlights that miRNA-455 targets might have a pleiotropic role in both cartilage and bones.


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