The novel tRF-23 promotes osteogenic differentiation of hBMSCs and protects against bone loss in ovariectomized mice.

Abstract

The pathogenesis of osteoporosis is closely related to the impaired human bone marrow-derived stromal cells (hBMSCs) osteogenic differentiation. No studies to date, however, have established whether tRNA-derived fragments (tRFs) can influence osteogenic differentiation of hBMSCs or the onset of osteoporosis. Here, tRF-23 was found to control hBMSC osteogenesis through its ability to target suppressor of cytokine signaling 1 (SOCS1) via the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. tRF-23 was then further established as a potential target for efforts to protect against bone loss and marrow adipose tissue (MAT) accumulation in osteoporotic model mice, and its molecular mechanism was also verified in vivo. Together, these results suggest a model in which tRF-23 can protect against bone loss induced by ovariectomized (OVX) through the augmentation of hBMSC osteogenesis, providing a foundation for characterizing the pathogenesis of osteoporosis and seeking new therapeutic targets for this disruptive condition.