MiR-133a delivery to osteoblasts ameliorates mechanical unloading-triggered osteopenia progression in vitro and in vivo.

Mechanical unloading-induced bone loss is a clinical challenge, and deep understanding for this disease is necessary for developing novel and effective therapies. MicroRNAs (miRNAs) are small non-coding RNAs, and involved in bone remodeling. In the study, we attempted to explore the potential of miR-133a in regulating osteoblast activation and its anti-osteopenia function both in vitro and in vivo. Our in vitro studies at first showed that miR-133a could significantly promote the expression of osteocalcin (OCN), Collagen I, alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and osterix (Osx), promoting the activation and mineralization of osteoblasts. Then, hindlimb unloading (HU)-challenged mice were established with or without intravenous injection of agomir-miR-133a using an osteoblast-targeting delivery system. We found that miR-133a in osteoblasts significantly alleviated the bone loss, microstructural, and biomechanical property in mice with mechanical unloading, contributing to osteopenia alleviation. Furthermore, both in vitro and in vivo experiments showed that miR-133a could restrain osteoclastogenesis via tartrate-resistant acid phosphatase (TRAP) staining. In conclusion, our results suggested that miR-133a may be a promising factor in mediating the occurrence and progression of osteopenia caused by mechanical unloading, and thus targeting miR-133a could be considered as an effective therapeutic strategy for the suppression of pathological osteopenia.