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Review
. 2022 Sep 8:13:992476.
doi: 10.3389/fphar.2022.992476. eCollection 2022.

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Zhichao Li  1 , Yan Wu  2 , Guoqing Tan  3 , Zhanwang Xu  3 , Haipeng Xue  1   3
Affiliations
Review

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Zhichao Li et al. Front Pharmacol. .

Abstract

Low back pain has been found as a major cause of global disease burden and disability. Intervertebral disc degeneration is recognized as the vital factor causing low back pain. Intervertebral disc degeneration has a complex mechanism and cannot be avoided. Traditional strategies for the treatment of intervertebral disc degeneration cannot meet the needs of intervertebral disc regeneration, so novel treatment methods are urgently required. Exosomes refer to extracellular vesicles that can be released by most cells, and play major roles in intercellular material transport and information transmission. MicroRNAs have been identified as essential components in exosomes, which can be selectively ingested by exosomes and delivered to receptor cells for the regulation of the physiological activities and functions of receptor cells. Existing studies have progressively focused on the role of exosomes and exosomal microRNAs in the treatment of intervertebral disc degeneration. The focus on this paper is placed on the changes of microenvironment during intervertebral disc degeneration and the biogenesis and mechanism of action of exosomes and exosomal microRNAs. The research results and deficiencies of exosomes and exosomal microRNAs in the regulation of apoptosis, extracellular matrix homeostasis, inflammatory response, oxidative stress, and angiogenesis in intervertebral disc degeneration are primarily investigated. The aim of this paper is to identify the latest research results, potential applications and challenges of this emerging treatment strategy.

Keywords: exosomal miRNA; exosome; intervertebral disc degeneration; microRNA; regenerative medicine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Anatomy of a normal IVD. The IVD consists of a central NP, an AF surrounding the NP, and a CEP connecting the upper and lower cones. The extracellular matrix of NP is mainly composed of proteoglycans and type II collagen. AF is divided into two parts, the content of type I collagen gradually decreases from outside to inside, and type II collagen gradually increases. CEP confines NP and AF within the anatomical boundaries, consisting mainly of proteoglycans and type II collagen.
FIGURE 2
FIGURE 2
Pathological changes in degenerated IVD. NCs, notochord cells; NPCs, nucleopulpocytes; AF, annulus fibrosus; CEP, cartilage endplate; ECM, extracellular matrix; HIFs, hypoxia-inducible factors; MMPs, metalloproteinases; ADAMTs, metalloproteinase with thrombospondin motifs; TIMPs, tissue inhibitors of metalloproteinases; CTGF, connective tissue growth factor; VEGF, vascular endothelial growth factor; NGF, nerve growth factor; BDNF, brain-derived neurotrophic factor; IL-1,6,8, interleukin-1,6,8; PGE2, prostaglandin E2; TNF-α, tumor necrosis factor; IFN-γ, interferon-gamma.
FIGURE 3
FIGURE 3
(A) Biogenesis of exosomes; (B) Composition of exosomes; (C) Internalization of exosomes; (D) Biogenesis of miRNAs. Pol II, RNA polymerase II; RNAP III, RNA polymerase III; (E) Mechanisms of miRNAs classification as exosomes: (a) miRISC-dependent pathway; (b) nMase-2-dependent pathway; (c) miRNA sequence motifs and guide proteins-dependent pathway; (d) 3′miRNA sequence-dependent pathway; (e) cellular availability of miRNAs.
FIGURE 4
FIGURE 4
(A) Strategies of exosomes as transport vehicles for endogenous and exogenous miRNA/miRNA mimics; (B) The sustained-release properties and good biocompatibility of hydrogels facilitating safe delivery and durable function of exosomes; (C) Surface-functionalized exosomes improving targeting specificity.
See this image and copyright information in PMC

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