MicroRNAs and Connexins in Bone: Interaction and Mechanisms of Delivery

Abstract

Purpose of review To describe the current knowledge on the cross-talk between connexins and microRNAs (miRs) in bone cells. Recent findings Connexins play a crucial role on bone development and maintenance, and disruptions in their abundance or localization can affect how bone perceives and responds to mechanical, hormonal, and pharmacological stimuli. Connexin expression can be modified by miRs, which modulate connexin mRNA and protein levels. Recently, different manners by which miRs and connexins can interact in bone have been identified, including mechanisms that mediate miR exchange between cells in direct contact through gap junctions, or between distant cells via extracellular vesicles (EVs). Summary We bring to light the relationship between miRs and connexins in bone tissue, with special focus on regulatory effects of miRs and connexins on gene expression, as well as the mechanisms that mediate miR exchange between cells in direct contact through gap junctions, or between distant cells via EVs.

Role of miRNAs in Melanoma Metastasis

“…The extracellular transfer of miRNAs is mediated by either protein transporters such as AGO (argonaute), HDL (high density lipoprotein), or extracellular vesicles (EV), e.g., oncosomes, ectosomes, exosomes, and melanosomes [33,47,48,49,50,51,52]. miRNA aggregation with proteins or encapsulation into EVs protect them from degradation by RNases [34,53,54,55]. Oncosomes (1–10 μm), first described in 2008 [56], are tumour-derived microvesicles that originate from membrane shedding of cancer cells, and their amount is associated with tumour aggressiveness and progression [50,52].…”

“…Oncosomes (1–10 μm), first described in 2008 [56], are tumour-derived microvesicles that originate from membrane shedding of cancer cells, and their amount is associated with tumour aggressiveness and progression [50,52]. Ectosomes (50–2000 nm) are formed through the outward budding of the plasma membrane [53]. Exosomes, which are the smallest type of EVs (30–180 nm in diameter), were discovered by Pan and Johnstone in 1983 [57], and originate from intracellular endosomes that subsequently form multivesicular bodies (MVBs) that are released from donor cells upon fusion with the plasma membrane [58,59].…”

“…Intercellular miRNA transport mediated via EVs includes: fusion, endocytosis, phagocytosis, and receptor mediated uptake. AGO-bound miRNAs have been shown to pass between adjacent cells via gap junctions or through hemichannels (HC) into the extracellular space to enter the target cell [53]. Transporters such as ABCA1 (ATP-binding cassette transporter 1) mediate the release of HDL–miRNA complexes that are taken up by recipient cells via SR-B1 (scavenger receptor class B type 1) [64].…”

TLR4 knockdown by miRNA-140-5p improves tendinopathy: an in vitro study

“…TGF-β1 overexpression first results in TLR4/NF-κB signaling pathway activation. Furthermore, this may bring about increasing fibrosis and apoptosis [21][22][23]. As proven by experiments in this study, due to stimulation from TGF-β1, Figure 10.…”

Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease

“…Cx43 can also influence the expression of miRNAs themselves, notably miR-21 in osteocytes, a pathway linked to osteocyte apoptosis and osteoclast formation/recruitment [ 93 ]. Moreover, direct transfer of miRNAs—through gap junctions—has been described, and is thought to play a role in bone development [ 94 ] as well as in aspects of tumor growth and tumor dormancy [ 3 ].…”