Multiple mechanisms are implicated in the development of primary osteoarthritis (OA), in which genetic and
epigenetic factors appear to interact with environmental factors and age to initiate the disease and stimulate its progression.
Changes in expression of microRNAs (miRs) contribute to development of osteoarthritis. Numerous miRs are involved
in cartilage development, homeostasis and degradation through targeting genes expressed in this tissue. An important
regulator of gene expression in human cartilage is miR-140, which directly targets a gene coding aggrecanase
ADAMTS-5, that cleaves aggrecan in cartilage. This miR is considered a biological marker for cartilage and its level significantly
decreases in OA cartilage. On the other hand, increased expression of miR-146a in early OA inhibits two other
cartilage-degrading enzymes: MMP13 and ADAMTS4, and may provide a useful tool in developing treatments for OA.
The COL2A1 gene, encoding collagen type II, which is the most abundant structural protein of the cartilage, is silenced by
miR-34a and activated by miR-675. Every year, new targets of cartilage miRs are validated experimentally and this opens
new possibilities for new therapies that control joint destruction and stimulate cartilage repair. At the same time development
of next-generation sequencing technologies allows to identify new miRs involved in cartilage biology.