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.

Abstract

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.

Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.7K
Overview of Exosomes01:36

Overview of Exosomes

Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
3.4K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.7K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.6K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
40.0K