Migrasomal miRNA reduces bone loss in mouse osteoporosis model

In a preclinical study, pre-osteoblast-derived migrasomes reduced bone loss in ovariectomized mice by delivering miR-21a-5p, which inhibited osteoclast differentiation in cell experiments through the Myc/MAPK/ERK signaling axis, the researchers report. The extracellular vesicles did not directly affect osteoblast differentiation, suggesting that the effect was directed toward the bone-resorbing side of bone remodeling. The study provides proof-of-concept for migrasome-associated microRNA signaling as a possible route of communication between osteoblasts and osteoclasts.

Migrasomes are migration-dependent extracellular vesicles released along retraction fibers of migrating cells. To investigate their role in osteoporosis, the team examined osteoporotic bone tissue using immunofluorescence and Western blotting. Osteoblast-related migrasome markers were markedly downregulated in the affected tissue.

The investigators also re-analyzed publicly available single-cell RNA-sequencing datasets of human bone to identify cellular sources associated with altered migrasome signatures. The researchers characterized migrasomes derived from pre-osteoblasts with electron microscopy, nanoparticle tracking analysis, Western blotting and high-throughput microRNA sequencing. In these in vitro experiments, pre-osteoblast-derived migrasomes delivered miR-21a-5p and inhibited osteoclast differentiation.

The microRNA targeted Myc and blocked the MAPK/ERK signaling axis. Under the tested conditions, the vesicles did not directly affect osteoblast differentiation, supporting an effect on osteoclast development rather than a general suppression of osteoblast activity. The team subsequently tested the approach in an ovariectomy-induced osteoporosis mouse model.

Animals received tail-vein injections of either pre-osteoblast-derived migrasomes or miR-21a-5p agomiR. Both treatments significantly improved bone microarchitecture and alleviated ovariectomy-associated bone loss. These animal results show the measured effects of the two interventions, but they do not by themselves establish that the improved bone architecture in mice arose specifically from miR-21a-5p transfer inside migrasomes or from the Myc/MAPK/ERK mechanism observed in cultured cells.

The evidence remains preclinical: the functional and mechanistic experiments were conducted in mouse cell cultures, and the therapeutic interventions were tested in an ovariectomy mouse model, not in people with osteoporosis. The human bone single-cell datasets were analyzed to help identify cellular associations, whereas no clinical efficacy, safety or dosing conclusions were established. The authors therefore characterize the work as proof-of-concept for miR-21a-5p as a potential therapeutic target and for migrasome-mediated intercellular signaling as a subject for further osteoporosis research.

Subject of Research: Preclinical testing of migrasomal miR-21a-5p in osteoclast differentiation and osteoporosis-related bone loss

Article Title: Pre-osteoblast-derived migrasomal miR-21a-5p inhibits osteoclast differentiation via the Myc/MAPK/ERK axis to alleviate osteoporosis

Article References: Yu, H., Liu, X., Huang, F., Hu, L., & Wang, Y. (2026). Pre-osteoblast-derived migrasomal miR-21a-5p inhibits osteoclast differentiation via the Myc/MAPK/ERK axis to alleviate osteoporosis. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-09108-8

Image Credits: AI Generated

DOI: 10.1186/s12967-026-09108-8

Keywords: osteoporosis, migrasomes, miR-21a-5p, osteoclast differentiation, osteoblasts, bone loss, extracellular vesicles, MAPK/ERK signaling, Myc, mouse model, Pre-osteoblast-derived, migrasomal