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Published on: October 6, 2023
Emerging roles of microRNAs as extracellular vesicle cargo secreted from osteoblasts
Yuji Yoshiko1, Tomoko Minamizaki1
1Department of Calcified Tissue Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Background:
Extracellular vesicles (EVs) have come into the spotlight as messengers, delivering cargo for cell-cell communication. Concomitantly, increasing attention has been focused on microRNAs (miRNAs) as EV cargo. Besides their well-known role in extracellular matrix mineralization, whether matrix vesicles (MVs) - which are in a broad sense a class of EV - also deliver miRNAs to regulate the function of recipient cells remains unclear.
Highlight:
We recently found that MVs budding from osteoblasts contain many miRNAs that can be transferred to the bone matrix. Of these, miR-125b was released into the bone marrow microenvironment during bone resorption, where it targeted the transcriptional repressor Prdm1 in osteoclast precursors, resulting in increased expression of anti-osteoclastogenic factors and suppression of osteoclastogenesis, thereby increasing bone mass in mice.
Conclusion:
Beyond their well-established action in bone mineralization, MVs play a role in the transport of miRNAs from osteoblasts into the bone matrix. Similar to the miR-125b axis in osteoclastogenesis, it seems likely that other miRNAs that accumulate in bone via MV transport may also act as mediators of cell-cell communication in the skeletal system.
Insights
Matrix vesicles (MVs) transport microRNAs (miRNAs) into bone, regulating bone mass. MiR-125b delivered by MVs suppresses osteoclastogenesis, increasing bone mass in mice.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Extracellular vesicles (EVs) mediate cell-cell communication.
- MicroRNAs (miRNAs) are key cargo within EVs.
- The role of matrix vesicles (MVs), a class of EVs, in miRNA transport and recipient cell regulation is largely unknown.
Purpose of the Study:
- To investigate the role of MVs in transporting miRNAs within the bone matrix.
- To determine if MVs deliver functional miRNAs that regulate bone cell function.
Main Methods:
- Analysis of miRNA content in MVs derived from osteoblasts.
- Investigating the transfer of MVs and their miRNA cargo to the bone matrix.
- Assessing the impact of specific miRNAs on osteoclast precursor cells and osteoclastogenesis in vivo.
Main Results:
- MVs budding from osteoblasts contain numerous miRNAs, which are transferred to the bone matrix.
- miR-125b was identified as a key miRNA released from MVs into the bone marrow microenvironment.
- In vivo, miR-125b targeted Prdm1 in osteoclast precursors, suppressing osteoclastogenesis and increasing bone mass in mice.
Conclusions:
- MVs are involved in transporting miRNAs from osteoblasts into the bone matrix, extending their known function beyond mineralization.
- The miR-125b/Prdm1 axis demonstrates a novel mechanism of miRNA-mediated cell-cell communication in the skeletal system.
- Other miRNAs transported by MVs likely play significant roles in skeletal biology and cell communication.
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