MicroRNA Contents in Matrix Vesicles Produced by Growth Plate Chondrocytes are Cell Maturation Dependent

Abstract

Chondrocytes at different maturation states in the growth plate produce matrix vesicles (MVs), membrane organelles found in the extracellular matrix, with a wide range of contents, such as matrix processing enzymes and receptors for hormones. We have shown that MVs harvested from growth zone (GC) chondrocyte cultures contain abundant small RNAs, including miRNAs. Here, we determined whether RNA also exists in MVs produced by less mature resting zone (RC) chondrocytes and, if so, whether it differs from the RNA in MVs produced by GC cells. Our results showed that RNA, small RNA specifically, was present in RC-MVs, and it was well-protected from RNase by the phospholipid membrane. A group of miRNAs was enriched in RC-MVs compared RC-cells, suggesting that miRNAs are selectively packaged into MVs. High throughput array and RNA sequencing showed that ~39% miRNAs were differentially expressed between RC-MVs and GC-MVs. Individual RT-qPCR also confirmed that miR-122-5p and miR-150-5p were expressed at significantly higher levels in RC-MVs compared to GC-MVs. This study showed that growth plate chondrocytes at different differentiation stages produce different MVs with different miRNA contents, further supporting extracellular vesicle miRNAs play a role as “matrisomes” that mediate the cell–cell communication in cartilage and bone development.

The Role of MicroRNAs in Influencing Body Growth and Development

“…Functional analysis showed that these miRNAs influenced key functions for cartilage development and extracellular matrix control such as stem cell regulation, focal adhesion, and cell cycle control. These data further support the evidence that extracellular miRNAs play a key role for cell-cell communication and cell proliferation and differentiation in the growth plate [37].…”

Circulating microRNAs as potential diagnostic biomarkers for osteoporosis

“…For miR-122-5p, The Human miRNA Tissue Atlas 26 (website https://ccb-web.cs.uni-saarland.de/tissueatlas/ ) Variance Stabilised Normalisation (VSN) relative data 27 showed that miR-122-5p is expressed in liver and bone, as well as a number of other tissues, but hardly present in bone marrow. However, recently, it has been reported in rats that microvesicles produced by resting zone chondrocytes are over 800-fold enriched in hsa-miR-122-5p than the producing cells 28 , whereas miR-122-5p is not present in microvesicles from growth zone chondrocytes. This observation raises the novel possibility that the changes in serum hsa-miR-122-5p levels in osteoporosis/osteopaenia patients might reflect changes in chondrocyte-derived microvesicles in the blood.…”

Lipoproteins in Cardiovascular Calcification: Potential Targets and Challenges

“…Matrix vesicles also mediate a wide range of functions besides initiation of mineralization, such as cell-cell communication, depending on their distinct contents and properties. These may include different microRNA species (miR-122-5p vs. miR-150-5p), different specific phospholipids, different activities of alkaline phosphatase and phospholipase A2, different membrane stiffness, and different membrane receptors ( 116 ). Due to these distinct functions and properties, matrix vesicles are now described by a wide variety of names: microvesicles, extracellular membrane vesicles, ectosomes, extracellular vesicles, microparticles, and exosomes, depending on cells of origin, tissue location, and the investigator's field of science.…”