miRNA-146A plays key role in bone metabolism and osteoporosis

Micro RNAs (miRNAs) play a crucial role in various cellular functions of the human body. A good example of their importance is miR-146a, an important anti-inflammatory miRNA. This was found to negatively impact osteogenesis and bone regeneration in vitro, by controlling the differentiation of mesenchymal stem cells.

The influence of miR-146a on bone stability as well as the development of osteoporosis and remodelling has not been fully delineated. Saferding et al. analysed the role of mIR-146a in bone metabolism by assessing systemic bone, tibiae, and femur of wildtype and miR-146a deficient mice (3 to 18 months of age) with histological and µCT analysis. Serum cytokine levels were analysed by ELISA, and miRNA expression levels in bone were analysed by qPCR. Ovariectomy induced bone loss was performed to induce osteoporosis. Significantly increased trabecular bone mass was seen in miR-146a deficient mice compared to wildtype animals, starting from 6 months of age, while cortical thickness of systemic bones was significantly reduced. Analysis of serum in aged miR-146a deficient animals showed elevated activity of bone-resorbing osteoclasts compared to wildtype animals. qPCR results showed elevated expression of signature molecules of osteoclasts as well as osteoblasts in aged miR-146a deficient mice, suggesting a regulatory role of miR-146a in both cell types.

Histological analysis of long bones showed significant trabecular bone loss in ovariectomised wildtype mice. However, there was no trabecular bone loss in ovariectomised miR-146a deficient animals. It was concluded by the researchers that miR-146a controls bone turnover and miR-146a deficient mice build up bone over time. Furthermore, the loss of miR-146a protects bone loss induced by oestrogen deficiency, which suggests that miR-146a may be used as a potential therapeutic target in the treatment of osteoporosis.[3]