Role of non‑coding RNAs in cartilage endplate (Review)
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- Published online on: May 11, 2023 https://doi.org/10.3892/etm.2023.12011
- Article Number: 312
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Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
1. Introduction
At present, the incidence of non-specific neck and lower back pain in the global population is high and the etiology is complex (1,2); this seriously affects the quality of life or even causes disability in affected individuals, reduces life expectancy and increases the economic and social burden (3,4). The total annual expenses associated with lower back pain were ~£12 billion in the UK in 1998(5), and US$7.4 billion in the USA from 1997 to 2007(6). Moreover, the total annual costs associated with neck pain were US$686 million in The Netherlands in 1996(7). Efforts have been made by researchers and clinicians to elucidate the pathogenesis of neck and lower back pain and promote treatment strategies (8,9). One of the main pathogenic factors of these afflictions is intervertebral disc degeneration (IDD) (10-13). Currently, various intervention measures are available for chronic musculoskeletal pain, including psychological based therapies (14-20), pharmacological treatments (21-24), and physical-based therapies (20,25-27). However, satisfactory results have not been achieved in terms of pain relief and functional improvement using these methods.
In recent years, various novel interventions have been used to explore the treatment of IDD, such as stem cell transplantation (28), and nanoparticles (29). At present, stem cell therapy for IDD includes hematopoietic precursor stem cells (30), mesenchymal stem cells (MSCs) and adipose-derived stem cells (31). Among them, MSCs have been well studied, including autologous and allogeneic MSCs. In 2011, Orozco et al (32) used autologous MSCs transplantation to treat IDD and showed some pain relief. In 2017, they further used allogeneic MSCs to treat IDD, confirming the feasibility and safety of this method and having some pain relief (33). However, the treatment of IDD with stem cells has yet to achieve satisfactory outcomes, possibly due to unclear treatment mechanisms, low survival rates of stem cells, different sources and injection methods of stem cells and a lack of large-scale clinical studies. Recently, nanoparticles have been increasingly used to treat IDD. Prussian blue nanoparticles relieve intracellular oxidative stress and increases the activity of intracellular antioxidant enzymes to rescue IDD (34); polydopamine nanoparticles alleviate IDD by reactive oxygen species consumption, iron chelation and glutathione peroxidase-4 ubiquitination inhibition (29). However, these treatments remain in vitro or have been tested in animal models and not in appropriate IDD models. Bioreactors are culture systems that can mimic the physiological environment of the IDD and provide an accurate nutritional and mechanical environment for the culture of intervertebral discs (IVD) organs (35). However, current cultivation techniques do not allow for extended reactor cultivation time. According to the research conducted by Šećerović et al, the survival rate of fibrous rings decreases by >30% within 3 weeks (35). Additionally, there are still significant differences between the simulated physiological state of the IVD in the current IVD bioreactor and the actual human IVD. Therefore, there are still significant limitations in the research and treatment of IDD using bioreactors.
IVDs are often referred to as the largest avascular structures of the human body (36), which consist of gelatinous nucleus pulposus (NP) as the central structure, surrounded by lamellar annulus fibrosus (AF) and sandwiched by the superior and inferior cartilage endplate (CEP) (37,38). Due to the avascular nature of the IVD, small molecules (such as nutrients) have to reach the cells through the extracellular matrix (ECM) mainly by diffusion (39), from the blood vessels at disc margins via two pathways: The CEP-NP pathway and the AF periphery pathway. Several researchers have reported that the CEP-NP nutritional pathway is primarily responsible for nurturing cells in the NP and inner AF regions, while the AF periphery is mainly for cells in the outer AF region (40-42) (Fig. 1). CEP degeneration can hinder the transport of nutrients and causes the dysfunctions of NP and CEP cells (43-45), including senescence, apoptosis and aberrant cell proliferation. Thus, CEP degeneration is considered one of the major causes of IDD, which causes neck or lower back pain (46-48). At present, there are numerous clinical treatments available for neck and lower back pain; however, these treatments can only partially improve some symptoms of patients and cannot fundamentally delay or reverse the pathological process of IDD (49,50). Therefore, restoring the biological function of the CEP and the nutrient supply of IVD, and preventing or even reversing CEP degeneration at the molecular level are the new aims of treatment for neck and lower back pain.
Non-coding RNAs (ncRNAs) are present in the majority of tissues of different species and account for 99% of the total RNA content (51-54). In addition, ncRNAs, DNA methylation and histone modifications are the main mechanisms in epigenetics (55,56). They have been defined as a class of RNA molecules transcribed from the genome, but not encoding proteins, such as long ncRNAs (lncRNAs) (57,58), microRNAs (miRNAs/miRs) (59,60) and circular RNAs (circRNAs) (61-63), with known biological functions, as well as unknown functions (64). ncRNAs have been found to be involved in the development of various diseases, including cancer, heart failure and even nervous system diseases (65-67). Notably, an increasing number of studies have demonstrated that ncRNAs are involved in chondrocyte degeneration through multiple mechanisms (68,69) (Fig. 2).
2. miRNAs and CEP
Profile and mechanisms of miRNAs in CEP
Previously, it has been determined that miRNAs play a critical role in complex gene regulatory networks (70). According to statistics, >1,500 miRNAs have been found in the human genome, and each miRNA can target multiple mRNAs; in addition, each mRNA can also be regulated by several miRNAs (71-73). Short RNA molecules of 19-25 nucleotides in size are a class of ncRNAs that regulate the post-transcriptional silencing of target genes by directly binding to the 3'-untranslated region (UTR), 5'-UTR and coding sequence regions of their target mRNAs (74). The majority of miRNA sequences are conserved across species (75). However, miRNA expression varies depending on the time and period examined and tissue type, which indicates that changes in miRNA expression may reflect different cellular composition or activation states (76,77). There is evidence to indicate that miRNAs participate in diverse chondrocyte processes, such as cell proliferation (78), apoptosis (79) and differentiation (80). They are therefore involved in a wider range of processes, such as cartilaginous development, degeneration (81) and regeneration (82). Consequently, CEP degeneration is the primary factor leading to IDD and maintaining the physiological function of CEP is essential for prevention and treatment of IDD (46).
Previous studies have demonstrated that intermittent cyclic mechanical tension (ICMT) can lead to CEP degeneration (83,84). However, the role of miRNAs in regulating chondrocyte responses to ICMT needs to be elucidated. In the study by Feng et al (85), CEP chondrocytes from patients without ICMT stimulation were used as controls and specimens were obtained from patients who underwent posterior discectomy and a fusion procedure for IDD. They identified a total of 21 significantly upregulated and 62 downregulated identified compared with the control.
The biological potency of miRNAs has been well-established, with their regulatory effects primarily exerted through sponge target genes, as depicted in Fig. 2, which illustrates the underlying molecular mechanisms.
Roles of miRNAs in CEP
miRNAs are involved in the regulation of multiple mechanisms as a novel subtype ncRNAs. There is evidence to indicate that the apoptosis of chondrocytes in the CEP is implicated in the pathogenesis IDD. Chen et al (86) demonstrated that the expression of miR-34a is markedly elevated in human degenerated CEP chondrocytes compared with normal CEP chondrocytes. Furthermore, luciferase assays from the same study indicated that Bcl-2 is a target of miR-34a, while miR-34a represses the expression of Bcl-2. Functionally, the inhibition of miR-34a rescues the fas-induced apoptosis of CEP chondrocytes by releasing Bcl-2, which plays an important role in the development of IDD.
It has been shown that miRNAs are involved in the tension-induced degeneration of endplate chondrocytes by regulating the miR-455-5p/runt-related transcription factor 2 (RUNX2) axis. In the majority of cases, more tension is borne by endplate chondrocytes compared with other cells in human body (87), which is responsible for chondrocyte degeneration (88,89). In chondrocytes, the aberrantly low-expression of miR-455-5p increases the degeneration level of chondrocytes by upregulating RUNX2 expression using ICMT. Furthermore, Xiao et al (90) revealed that the up- or downregulation of miR-455-5p does not affect the proliferation or apoptosis of endplate chondrocytes, while RUNX2 expression also exhibits a down- and upregulation, respectively. Therefore, these findings result indicate that miR-455-5p is a therapeutic target for tension-induced degeneration. There is previous evidence to indicate that miRNAs are involved in the calcification of CEP chondrocytes induced by matrix stiffness. For example, it has been shown that the inhibition of miR-20a attenuates calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhances the calcification of CEP chondrocytes on a stiff matrix, which is positively associated with the degree of IDD (91).
The role of CEP chondrocytes in ECM synthesis and catabolism, such as collagens and proteoglycans, plays an important role in maintaining the structural stability of the IVD and in resisting mechanical loads (92,93). In patients with IDD, an imbalance in matrix synthesis and breakdown in the CEP is observed, as shown by the increased expression of breakdown proteins, such as MMP-3 and MMP-9, and a corresponding reduction in the expression of synthetic proteins. Sheng et al (94) found that the overexpression of miR-221 in degenerative CEP tissue accelerates apoptosis by downregulating the level of estrogen receptor α. Furthermore, the increased level of miR-221 deteriorates the degradation of the ECM by disrupting the balance in the expression of ECM-degrading and anti-ECM-degrading genes.
Recent studies have demonstrated that cartilage endplate stem cells (CESCs) can maintain the normal function of the NP and CEP through miRNAs. Chen et al (95) revealed that miR-637 is expressed in low levels in the degenerative CEP, and the inhibition of miR-637 promotes the osteogenic differentiation ability of degenerative CESCs. However, the upregulation of Wnt family member 5A partially annuls the inhibitory effects of miR-637 overexpression on the osteogenic differentiation of degenerative CESCs. In addition, Chen and Jiang (96) examined the effects of normal CESC-derived exosomes on autophagy, apoptosis and ECM metabolism in the NP. Bioinformatics analysis was used to analyze differences in miRNA expression, and dual-luciferase reporter assays were used to detect target associations. They confirmed that exosomes-derived miR-125-5p from CESCs regulate autophagy and ECM metabolism in the NP by targeting SUV38H1.
There is evidence to indicate that the reduction of the proliferation of CEP chondrocytes is implicated in the pathogenesis of IDD. Using a double luciferase assay, Wang et al (97) indicated that the target gene of miR-142-3p is high mobility group box 1 (HMGB1), the expression of which is significantly increased during the process of IDD. Functionally, the inhibition of chondrocytes proliferation ability follows the addition of a HMGB1 inhibitor.
In conclusion, the aberrant expression of seven miRNAs has been discovered to be involved in various cellular processes, such as proliferation, apoptosis and calcification-induced apoptosis, with their specific regulatory mechanisms and expressions documented in Table I.
3. lncRNAs and CEP
Profile and mechanism of lncRNAs in CEP
From the discovery of the first ncRNA in bacteria in 1980(98) to a few long-stranded ncRNAs, such as H19 and Xist characterized in the pre-genomic era, to the entry of the genomic era in the 21st century, immense progress has been made in the depth and breadth of research into lncRNAs (99). Previously, lncRNAs were considered as biologically non-functional transcriptional ‘noise’ (100). However, at present, lncRNAs are considered important regulatory factors with multiple biological functions (99,101), which cannot be translated into protein. The expression patterns of various lncRNAs regulate the different phenotypes of cells (102). In addition, lncRNAs function through a variety of mechanisms, such as acting as a scaffold, bait, signal and guide (103). Of note, lncRNAs play the role of competitive endogenous RNAs (ceRNAs) or small interfering RNA and participate in the lncRNA/circRNA/miRNA/mRNA network as transcriptional regulators (104), which mainly regulate gene expression or control signaling pathways by competitively inhibiting or destroying specific miRNAs (105,106). LncRNAs play an important role in various life processes of organisms, including the cell cycle (101,107-109), differentiation (110-112), and metabolism (57). Furthermore, they participate in the occurrence and development of diseases by affecting gene expression (113), chromatin structure (114) and cell signaling pathways (115).
It has been shown that there is a clear difference in lncRNA expression between degenerated endplate chondrocytes and normal endplate chondrocytes (116). In 2020, the expression profile of lncRNAs was reported for the first time in the endplate of degenerated cartilage. In degenerated chondrocytes, 369 lncRNAs exhibited a differential expression, including 316 upregulated and 53 downregulated lncRNAs, contrasting with the non-degenerated CEP of cervical fractures. In addition, Li et al (117) identified the highly selective expression of 34 lncRNAs in human fetal growth plate chondrocytes by employing RNA sequencing. A total of eight lncRNAs were adjacent to the loci of protein coding genes that participate in skeletal development, suggesting that cartilage-selective lncRNAs may be involved in chondrogenesis is through the regulation of protein coding genes.
In summary, the biological functions of lncRNA in chondrocytes can be mediated by various mechanisms, including miRNA sponging, protein scaffolding and translational regulation. Additionally, specific expression patterns of lncRNAs in degenerated endplate chondrocytes have been demonstrated.
Roles of lncRNAs in CEP
Evidence suggests that diabetes causes CEP degeneration by altering endplate thickening and reducing porosity (118-121). Furthermore, chondrocyte apoptosis, characterized by various signaling molecules, is involved in the degeneration of CEPs (122,123). Based on these findings, Jiang et al (124) induced CEP cell degeneration with high-glucose medium and revealed that the knockdown of lncRNA MALAT1 reduces the apoptosis of chondrocytes. Furthermore, they demonstrated that lncRNA MALAT1 promotes high glucose-induced rat CEP apoptosis via the p38/MAPK signaling pathway. lncRNAs, as gene expression modulators, are expected to be a novel target for the treatment of disc degeneration; however, to the best of our knowledge, studies on lncRNAs in CEP degeneration are limited and, thus, further studies on their mechanism of action in CEP degeneration are warranted.
4. circRNAs and CEP
Profile and mechanisms of circRNAs in CEP
circRNAs, which are single-stranded and covalently closed, were first reported as viroids (125), which are pathogens of certain plants in 1976 and were first detected in human HeLa cells by electron microscopy in 1979(126). Later on, with the development of high-throughput RNA sequencing and bioinformatics tools, circRNAs began to be considered as a general feature of the human transcriptome and are ubiquitous in numerous other metazoans, including mammals (127), unicellular eukaryotes (128), prokaryotes (129) and viruses (130). Previous studies have identified multiple functions of circRNAs, including serving as protein scaffolds or miRNA sponges and being translated into polypeptides (131,132). In addition, the unique covalently closed structure of circRNAs that provides them with a longer half-life and greater resistance to RNase R compared with linear RNAs (133), renders them as potential candidates for use as diagnostic biomarkers and therapeutic targets.
We previously conducted a study to compare degenerative CEP to healthy CEP using a human ceRNA microarray (134). It was revealed that 578 circRNAs were differentially regulated in degenerative CEP samples compared with healthy tissues. Of these, 435 circRNAs were highly expressed, while 143 were significantly repressed. In addition, it has been indicated that biomechanical stimulation is essential for the growth and maintenance of endplate cartilage function (102). Excessive mechanical loading, on the other hand, alters the distribution of the ECM in the CEP, ultimately leading to the destruction of normal cartilage structure and the interruption of nutrient supply (135). By applying an ICMT of 0.5 Hz and an extension of 10% to primitive human endplate chondrocytes, Xiao et al (136) verified upregulated expression levels of 17circRNAs and the downregulated expression of another 12 with fold changes 1.5 by using a circRNA microarray technique.
Compared with miRNAs and lncRNAs, circRNAs exhibit an enhanced richness, stability and specific expression (137). Furthermore, various mechanisms such as miRNA sponging, protein scaffolding and translational regulation can be utilized to regulate the chondrocyte process by circRNAs (138) (Fig. 2).
Roles of circRNAs in CEP
Specific circRNAs regulate the ECM and proliferation via a ceRNA mechanism, which contributes to the development of IDD (139). Specifically, circRNA_0058097 and circ small nucleolar RNA host gene 5 (SNHG5) are involved in ECM regulation (136,140). circSNHG5 is related to CEP cell proliferation. miR-495-3p stimulates ECM degradation and inhibits chondrocyte cell proliferation by inhibiting Cbp/P300-interacting transactivator with glu/asp rich carboxy-terminal domain 2, whereas circSNHG5 alleviates the negative effects by sponging miR-495-3p. However, in IDD tissues, the expression of circSNHG5 is repressed, resulting in an aberrantly higher level of miR-495-3p and IDD. The upregulation of circRNA_0058097 expression was observed in the loading group that was subjected to an ICMT of 0.5 Hz and 10% elongation degeneration. Furthermore, circRNA_0058097 can sponge miR-365a-5p and overexpression of miR-365a-5p alleviates tension-induced chondrocyte degeneration (130). These results suggest that the fate of CEP cells in IDD can be modulated by circRNAs, which have the potential to serve as therapeutic targets.
5. Conclusions and future perspectives
Neck and lower back pain is the most prevalent of all musculoskeletal conditions, and it places a major strain on individuals, health systems and social care systems (141). CEP degeneration is one of the primary causes of IDD that leads to neck and lower back pain (46). However, the mechanisms involved have not yet been fully elucidated. Recently, it has been shown that ncRNAs are involved in the degeneration of chondrocytes, including endplate chondrocytes (142).
The present review summarizes the latest evidence concerning the regulation of endplate chondrocytes in IDD based on miRNAs, lncRNAs and circRNAs. In addition, the present review summarizes the mechanisms through which proliferation, calcification, apoptosis and ECM degradation of the CEP can be regulated by regulating downstream target genes (Table I). The data presented herein provides novel insights into the etiology of endplate chondrocyte degeneration and identify ncRNAs as potential novel targets for the treatment of IDD. However, effective therapeutic approaches, such as bone/cartilage targeted hydrogel (143), and exosome-based bone-targeting (144), are hampered by an incomplete understanding of the mechanisms of CEP homeostasis and degeneration. Recently, the advent of novel materials like lipid nanoparticles and cationic polymers has enhanced the targeting specificity of therapy, while also mitigating toxicity and immunogenicity concerns. Furthermore, technological breakthroughs such as CRISPR/Cas gene editing have lowered off-target effects and boosted RNA interference levels. Therefore, injectable hydrogels or nanoparticles (145,146), recombinant adeno-associated viral vector-mediated gene delivery (147), and mesenchymal stem cell-based therapies (148) interfere with RNA expression in endplate chondrocytes to achieve the purpose of treating disc degeneration. At the same time, interfering with the central nodes in the regulatory network allows ncRNAs to provide a future for IDD treatment.
Acknowledgements
Not applicable.
Funding
Funding: The present study was supported by the National Natural Science Foundation of China (grant nos. 8166090137 and 8186090165), the National Natural Science Foundation of Jiangxi Province (grant no. 20202ACBL206012) and the Graduate Innovative Special Fund Projects of Jiangxi Province, China (grant no. YC2022-s212).
Availability of data and materials
Not applicable.
Authors' contributions
XKZ, JHY, JYJ, JZ, JHL, QC, TL, ZWW, HW, XXM, TLW, BL and XGC contributed to the conception and design of the study. JHL, QC, TL, ZWW and HW examined the relevant literature, and XKZ wrote the manuscript. JHY, JYJ, JZ, XXM TLW and BL provided advice and are responsible for revising the manuscript. All authors read and approved the final manuscript. Data sharing is not applicable.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet. 388:1545–1602. 2016.PubMed/NCBI View Article : Google Scholar | |
Minghelli B: Musculoskeletal spine pain in adolescents: Epidemiology of non-specific neck and low back pain and risk factors. J Orthop Sci. 25:776–780. 2020.PubMed/NCBI View Article : Google Scholar | |
Frymoyer JW and Cats-Baril WL: An overview of the incidences and costs of low back pain. Orthop Clin North Am. 22:263–271. 1991.PubMed/NCBI | |
Steenstra IA, Verbeek JH, Prinsze FJ and Knol DL: Changes in the incidence of occupational disability as a result of back and neck pain in the Netherlands. BMC Public Health. 6(190)2006.PubMed/NCBI View Article : Google Scholar | |
Maniadakis N and Gray A: The economic burden of back pain in the UK. Pain. 84:95–103. 2000.PubMed/NCBI View Article : Google Scholar | |
Dagenais S, Caro J and Haldeman S: A systematic review of low back pain cost of illness studies in the United States and internationally. Spine J. 8:8–20. 2008.PubMed/NCBI View Article : Google Scholar | |
Borghouts JAJ, Koes BW, Vondeling H and Bouter LM: Cost-of-illness of neck pain in The Netherlands in 1996. Pain. 80:629–636. 1999.PubMed/NCBI View Article : Google Scholar | |
Brockow T, Dillner A, Franke A and Resch KL: Analgesic effectiveness of subcutaneous carbon-dioxide insufflations as an adjunct treatment in patients with non-specific neck or low back pain. Complement Ther Med. 9:68–76. 2001.PubMed/NCBI View Article : Google Scholar | |
Miyamoto GC, Lin CC, Cabral CMN, van Dongen JM and van Tulder MW: Cost-effectiveness of exercise therapy in the treatment of non-specific neck pain and low back pain: A systematic review with meta-analysis. Br J Sports Med. 53:172–181. 2019.PubMed/NCBI View Article : Google Scholar | |
Nakamura M, Nishiwaki Y, Ushida T and Toyama Y: Prevalence and characteristics of chronic musculoskeletal pain in Japan. J Orthop Sci. 16:424–432. 2011.PubMed/NCBI View Article : Google Scholar | |
Nakamura M, Toyama Y, Nishiwaki Y and Ushida T: Prevalence and characteristics of chronic musculoskeletal pain in Japan: A second survey of people with or without chronic pain. J Orthop Sci. 19:339–350. 2014.PubMed/NCBI View Article : Google Scholar | |
Samartzis D, Karppinen J, Mok F, Fong DY, Luk KD and Cheung KM: A population-based study of juvenile disc degeneration and its association with overweight and obesity, low back pain, and diminished functional status. J Bone Joint Surg Am. 93:662–670. 2011.PubMed/NCBI View Article : Google Scholar | |
Gibson J, Nouri A, Krueger B, Lakomkin N, Nasser R, Gimbel D and Cheng J: Degenerative cervical myelopathy: A clinical review. Yale J Biol Med. 91:43–48. 2018.PubMed/NCBI | |
Slade SC and Keating JL: Unloaded movement facilitation exercise compared to no exercise or alternative therapy on outcomes for people with nonspecific chronic low back pain: A systematic review. J Manipulative Physiol Ther. 30:301–311. 2007.PubMed/NCBI View Article : Google Scholar | |
Furlan AD, Imamura M, Dryden T and Irvin E: Massage for low-back pain. Cochrane Database Syst Rev. (4)(Cd001929)2008.PubMed/NCBI View Article : Google Scholar | |
Hall J, Swinkels A, Briddon J and McCabe CS: Does aquatic exercise relieve pain in adults with neurologic or musculoskeletal disease? A systematic review and meta-analysis of randomized controlled trials. Arch Phys Med Rehabil. 89:873–883. 2008.PubMed/NCBI View Article : Google Scholar | |
Hendrick P, Te Wake AM, Tikkisetty AS, Wulff L, Yap C and Milosavljevic S: The effectiveness of walking as an intervention for low back pain: A systematic review. Eur Spine J. 19:1613–1620. 2010.PubMed/NCBI View Article : Google Scholar | |
Miller J, Gross A, D'Sylva J, Burnie SJ, Goldsmith CH, Graham N, Haines T, Brønfort G and Hoving J: Manual therapy and exercise for neck pain: A systematic review. Man Ther. 15:334–354. 2010.PubMed/NCBI View Article : Google Scholar | |
Rubinstein SM, van Middelkoop M, Assendelft WJ, de Boer MR and van Tulder MW: Spinal manipulative therapy for chronic low-back pain: An update of a Cochrane review. Spine (Phila Pa 1976). 36:E825–E846. 2011.PubMed/NCBI View Article : Google Scholar | |
van Middelkoop M, Rubinstein SM, Kuijpers T, Verhagen AP, Ostelo R, Koes BW and van Tulder MW: A systematic review on the effectiveness of physical and rehabilitation interventions for chronic non-specific low back pain. Eur Spine J. 20:19–39. 2011.PubMed/NCBI View Article : Google Scholar | |
Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C and Schoelles KM: Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev. 2010(Cd006605)2010.PubMed/NCBI View Article : Google Scholar | |
Chou R and Huffman LH: American Pain Society; American College of Physicians. Medications for acute and chronic low back pain: A review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 147:505–514. 2007.PubMed/NCBI View Article : Google Scholar | |
Roelofs PD, Deyo RA, Koes BW, Scholten RJ and van Tulder MW: Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. (1)(Cd000396)2008.PubMed/NCBI View Article : Google Scholar | |
Mason L, Moore RA, Edwards JE, Derry S and McQuay HJ: Topical NSAIDs for chronic musculoskeletal pain: Systematic review and meta-analysis. BMC Musculoskelet Disord. 5(28)2004.PubMed/NCBI View Article : Google Scholar | |
van Geen JW, Edelaar MJ, Janssen M and van Eijk JT: The long-term effect of multidisciplinary back training: A systematic review. Spine (Phila Pa 1976). 32:249–255. 2007.PubMed/NCBI View Article : Google Scholar | |
Scascighini L, Toma V, Dober-Spielmann S and Sprott H: Multidisciplinary treatment for chronic pain: A systematic review of interventions and outcomes. Rheumatology (Oxford). 47:670–678. 2008.PubMed/NCBI View Article : Google Scholar | |
Ravenek MJ, Hughes ID, Ivanovich N, Tyrer K, Desrochers C, Klinger L and Shaw L: A systematic review of multidisciplinary outcomes in the management of chronic low back pain. Work. 35:349–367. 2010.PubMed/NCBI View Article : Google Scholar | |
Sakai D and Andersson GB: Stem cell therapy for intervertebral disc regeneration: Obstacles and solutions. Nat Rev Rheumatol. 11:243–256. 2015.PubMed/NCBI View Article : Google Scholar | |
Yang X, Chen Y, Guo J, Li J, Zhang P, Yang H, Rong K, Zhou T, Fu J and Zhao J: Polydopamine nanoparticles targeting ferroptosis mitigate intervertebral disc degeneration via reactive oxygen species depletion, iron ions chelation, and GPX4 ubiquitination suppression. Adv Sci (Weinh). 10(e2207216)2023.PubMed/NCBI View Article : Google Scholar | |
Haufe SM and Mork AR: Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev. 15:136–137. 2006.PubMed/NCBI View Article : Google Scholar | |
Hoogendoorn RJ, Lu ZF, Kroeze RJ, Bank RA, Wuisman PI and Helder MN: Adipose stem cells for intervertebral disc regeneration: Current status and concepts for the future. J Cell Mol Med. 12:2205–2216. 2008.PubMed/NCBI View Article : Google Scholar | |
Orozco L, Soler R, Morera C, Alberca M, Sanchez A and Garcia-Sancho J: Intervertebral disc repair by autologous mesenchymal bone marrow cells: A pilot study. Transplantation. 92:822–828. 2011.PubMed/NCBI View Article : Google Scholar | |
Noriega DC, Ardura F, Hernandez-Ramajo R, Martín-Ferrero MÁ, Sánchez-Lite I, Toribio B, Alberca M, García V, Moraleda JM, Sánchez A and García-Sancho J: Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: A randomized controlled trial. Transplantation. 101:1945–1951. 2017.PubMed/NCBI View Article : Google Scholar | |
Zhou T, Yang X, Chen Z, Yang Y, Wang X, Cao X, Chen C, Han C, Tian H, Qin A, et al: Prussian blue nanoparticles stabilize SOD1 from ubiquitination-proteasome degradation to rescue intervertebral disc degeneration. Adv Sci (Weinh). 9(e2105466)2022.PubMed/NCBI View Article : Google Scholar | |
Šećerović A, Ristaniemi A, Cui S, Li Z, Soubrier A, Alini M, Ferguson SJ, Weder G, Heub S, Ledroit D and Grad S: Toward the next generation of spine bioreactors: Validation of an ex vivo intervertebral disc organ model and customized specimen holder for multiaxial loading. ACS Biomater Sci Eng. 8:3969–3976. 2022.PubMed/NCBI View Article : Google Scholar | |
Grunhagen T, Wilde G, Soukane DM, Shirazi-Adl SA and Urban JP: Nutrient supply and intervertebral disc metabolism. J Bone Joint Surg Am. 88 (Suppl 2):S30–S35. 2006.PubMed/NCBI View Article : Google Scholar | |
Song Y, Lu S, Geng W, Feng X, Luo R, Li G and Yang C: Mitochondrial quality control in intervertebral disc degeneration. Exp Mol Med. 53:1124–1133. 2021.PubMed/NCBI View Article : Google Scholar | |
Roughley PJ: Biology of intervertebral disc aging and degeneration: Involvement of the extracellular matrix. Spine (Phila Pa 1976). 29:2691–2699. 2004.PubMed/NCBI View Article : Google Scholar | |
Urban JP, Holm S and Maroudas A: Diffusion of small solutes into the intervertebral disc: As in vivo study. Biorheology. 15:203–221. 1978.PubMed/NCBI View Article : Google Scholar | |
Ogata K and Whiteside LA: 1980 Volvo award winner in basic science. Nutritional pathways of the intervertebral disc. An experimental study using hydrogen washout technique. Spine (Phila Pa 1976). 6:211–216. 1981.PubMed/NCBI | |
van der Werf M, Lezuo P, Maissen O, van Donkelaar CC and Ito K: Inhibition of vertebral endplate perfusion results in decreased intervertebral disc intranuclear diffusive transport. J Anat. 211:769–774. 2007.PubMed/NCBI View Article : Google Scholar | |
Rajasekaran S, Babu JN, Arun R, Armstrong BR, Shetty AP and Murugan S: ISSLS prize winner: A study of diffusion in human lumbar discs: A serial magnetic resonance imaging study documenting the influence of the endplate on diffusion in normal and degenerate discs. Spine (Phila Pa 1976). 29:2654–2667. 2004.PubMed/NCBI View Article : Google Scholar | |
Kang R, Li H, Ringgaard S, Rickers K, Sun H, Chen M, Xie L and Bünger C: Interference in the endplate nutritional pathway causes intervertebral disc degeneration in an immature porcine model. Int Orthop. 38:1011–1017. 2014.PubMed/NCBI View Article : Google Scholar | |
Yin S, Du H, Zhao W, Ma S, Zhang M, Guan M and Liu M: Inhibition of both endplate nutritional pathways results in intervertebral disc degeneration in a goat model. J Orthop Surg Res. 14(138)2019.PubMed/NCBI View Article : Google Scholar | |
Hutton WC, Murakami H, Li J, Elmer WA, Yoon ST, Minamide A, Akamaru T and Tomita K: The effect of blocking a nutritional pathway to the intervertebral disc in the dog model. J Spinal Disord Tech. 17:53–63. 2004.PubMed/NCBI View Article : Google Scholar | |
Jiang C, Guo Q, Jin Y, Xu JJ, Sun ZM, Zhu DC, Lin JH, Tian NF, Sun LJ, Zhang XL and Wu YS: Inhibition of EZH2 ameliorates cartilage endplate degeneration and attenuates the progression of intervertebral disc degeneration via demethylation of Sox-9. EBioMedicine. 48:619–629. 2019.PubMed/NCBI View Article : Google Scholar | |
Määttä JH, Kraatari M, Wolber L, Niinimäki J, Wadge S, Karppinen J and Williams FM: Vertebral endplate change as a feature of intervertebral disc degeneration: A heritability study. Eur Spine J. 23:1856–1862. 2014.PubMed/NCBI View Article : Google Scholar | |
Wang Y, Videman T and Battié MC: ISSLS prize winner: Lumbar vertebral endplate lesions: Associations with disc degeneration and back pain history. Spine (Phila Pa 1976). 37:1490–1496. 2012.PubMed/NCBI View Article : Google Scholar | |
Livshits G, Popham M, Malkin I, Sambrook PN, Macgregor AJ, Spector T and Williams FM: Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: The UK Twin Spine Study. Ann Rheum Dis. 70:1740–1745. 2011.PubMed/NCBI View Article : Google Scholar | |
Pennicooke B, Moriguchi Y, Hussain I, Bonssar L and Härtl R: Biological treatment approaches for degenerative disc disease: A review of clinical trials and future directions. Cureus. 8(e892)2016.PubMed/NCBI View Article : Google Scholar | |
Mattick JS: Non-coding RNAs: The architects of eukaryotic complexity. EMBO Rep. 2:986–991. 2001.PubMed/NCBI View Article : Google Scholar | |
Patrushev LI and Kovalenko TF: Functions of noncoding sequences in mammalian genomes. Biochemistry (Mosc). 79:1442–1469. 2014.PubMed/NCBI View Article : Google Scholar | |
Palazzo AF and Lee ES: Non-coding RNA: What is functional and what is junk? Front Genet. 6(2)2015.PubMed/NCBI View Article : Google Scholar | |
Watson CN, Belli A and Di Pietro V: Small Non-coding RNAs: New class of biomarkers and potential therapeutic targets in neurodegenerative disease. Front Genet. 10(364)2019.PubMed/NCBI View Article : Google Scholar | |
Braicu C, Calin GA and Berindan-Neagoe I: MicroRNAs and cancer therapy - from bystanders to major players. Curr Med Chem. 20:3561–3573. 2013.PubMed/NCBI View Article : Google Scholar | |
Cătană CS, Pichler M, Giannelli G, Mader RM and Berindan-Neagoe I: Non-coding RNAs, the Trojan horse in two-way communication between tumor and stroma in colorectal and hepatocellular carcinoma. Oncotarget. 8:29519–29534. 2017.PubMed/NCBI View Article : Google Scholar | |
Guo TF, Zhou MW, Li SH, Ye BL, Chen W and Fu ZB: Long non-coding RNA for metabolism of bone tissue. Zhongguo Gu Shang. 31:286–291. 2018.PubMed/NCBI View Article : Google Scholar : (In Chinese). | |
Wang J, Sun Y, Liu J, Yang B, Wang T, Zhang Z, Jiang X, Guo Y and Zhang Y: Roles of long non-coding RNA in osteoarthritis (Review). Int J Mol Med. 48(133)2021.PubMed/NCBI View Article : Google Scholar | |
Liu Q, Peng F and Chen J: The role of exosomal MicroRNAs in the tumor microenvironment of breast cancer. Int J Mol Sci. 20(3884)2019.PubMed/NCBI View Article : Google Scholar | |
Lan T, Shiyu-Hu Shen Z, Yan B and Chen J: New insights into the interplay between miRNAs and autophagy in the aging of intervertebral discs. Ageing Res Rev. 65(101227)2021.PubMed/NCBI View Article : Google Scholar | |
Guo HY, Guo MK, Wan ZY, Song F and Wang HQ: Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: A narrative review. Arthritis Res Ther. 22(270)2020.PubMed/NCBI View Article : Google Scholar | |
Wang T, Hao Z, Liu C, Yuan L, Li L, Yin M, Li Q, Qi Z and Wang Z: LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway. Cell Death Dis. 11(598)2020.PubMed/NCBI View Article : Google Scholar | |
Zhao R, Fu J, Zhu L, Chen Y and Liu B: Designing strategies of small-molecule compounds for modulating non-coding RNAs in cancer therapy. J Hematol Oncol. 15(14)2022.PubMed/NCBI View Article : Google Scholar | |
Matsui M and Corey DR: Non-coding RNAs as drug targets. Nat Rev Drug Discov. 16:167–179. 2017.PubMed/NCBI View Article : Google Scholar | |
Huang W, Li H, Yu Q, Xiao W and Wang DO: LncRNA-mediated DNA methylation: An emerging mechanism in cancer and beyond. J Exp Clin Cancer Res. 41(100)2022.PubMed/NCBI View Article : Google Scholar | |
Zhao Y, Ling S, Li J, Zhong G, Du R, Li Y, Wang Y, Liu C, Jin X, Liu W, et al: 3' untranslated region of Ckip-1 inhibits cardiac hypertrophy independently of its cognate protein. Eur Heart J. 42:3786–3799. 2021.PubMed/NCBI View Article : Google Scholar | |
Wu AC, Yang WB, Chang KY, Lee JS, Liou JP, Su RY, Cheng SM, Hwang DY, Kikkawa U, Hsu TI, et al: HDAC6 involves in regulating the lncRNA-microRNA-mRNA network to promote the proliferation of glioblastoma cells. J Exp Clin Cancer Res. 41(47)2022.PubMed/NCBI View Article : Google Scholar | |
Chen X, Gong W, Shao X, Shi T, Zhang L, Dong J, Shi Y, Shen S, Qin J, Jiang Q and Guo B: METTL3-mediated m(6)A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression. Ann Rheum Dis. 81:87–99. 2022.PubMed/NCBI View Article : Google Scholar | |
Chen J, Huang T, Liu R, Wang C, Jiang H and Sun H: Congenital microtia patients: The genetically engineered exosomes released from porous gelatin methacryloyl hydrogel for downstream small RNA profiling, functional modulation of microtia chondrocytes and tissue-engineered ear cartilage regeneration. J Nanobiotechnology. 20(164)2022.PubMed/NCBI View Article : Google Scholar | |
Li Z, Yu X, Shen J, Chan MT and Wu WK: MicroRNA in intervertebral disc degeneration. Cell Prolif. 48:278–283. 2015.PubMed/NCBI View Article : Google Scholar | |
Ambros V and Chen X: The regulation of genes and genomes by small RNAs. Development. 134:1635–1641. 2007.PubMed/NCBI View Article : Google Scholar | |
Krol J, Loedige I and Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 11:597–610. 2010.PubMed/NCBI View Article : Google Scholar | |
Zhu Y, Li K, Yan L, He Y, Wang L and Sheng L: miR-223-3p promotes cell proliferation and invasion by targeting Arid1a in gastric cancer. Acta Biochim Biophys Sin (Shanghai). 52:150–159. 2020.PubMed/NCBI View Article : Google Scholar | |
Lu TX and Rothenberg ME: MicroRNA. J Allergy Clin Immunol. 141:1202–1207. 2018.PubMed/NCBI View Article : Google Scholar | |
Rau CS, Yang JC, Wu SC, Chen YC, Lu TH, Lin MW, Wu YC, Tzeng SL, Wu CJ and Hsieh CH: Profiling circulating microRNA expression in a mouse model of nerve allotransplantation. J Biomed Sci. 20(64)2013.PubMed/NCBI View Article : Google Scholar | |
Guerau-de-Arellano M, Smith KM, Godlewski J, Liu Y, Winger R, Lawler SE, Whitacre CC, Racke MK and Lovett-Racke AE: Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. Brain. 134(Pt 12):3578–3589. 2011.PubMed/NCBI View Article : Google Scholar | |
Nie H, Zhang K, Xu J, Liao K, Zhou W and Fu Z: Combining bioinformatics techniques to study diabetes biomarkers and related molecular mechanisms. Front Genet. 11(367)2020.PubMed/NCBI View Article : Google Scholar | |
Shen P, Yang Y, Liu G, Chen W, Chen J, Wang Q, Gao H, Fan S, Shen S and Zhao X: CircCDK14 protects against Osteoarthritis by sponging miR-125a-5p and promoting the expression of Smad2. Theranostics. 10:9113–9131. 2020.PubMed/NCBI View Article : Google Scholar | |
Li S, Liu J, Liu S, Jiao W and Wang X: Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis. J Nanobiotechnology. 9(194)2021.PubMed/NCBI View Article : Google Scholar | |
Wu Z, Qiu X, Gao B, Lian C, Peng Y, Liang A, Xu C, Gao W, Zhang L, Su P, et al: Melatonin-mediated miR-526b-3p and miR-590-5p upregulation promotes chondrogenic differentiation of human mesenchymal stem cells. J Pineal Res. 65(e12483)2018.PubMed/NCBI View Article : Google Scholar | |
Chen L, Li Q, Wang J, Jin S, Zheng H, Lin J, He F, Zhang H, Ma S, Mei J and Yu J: MiR-29b-3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN. J Cell Mol Med. 21:3347–3359. 2017.PubMed/NCBI View Article : Google Scholar | |
Razmara E, Bitaraf A, Yousefi H, Nguyen TH, Garshasbi M, Cho WC and Babashah S: Non-Coding RNAs in cartilage development: An updated review. Int J Mol Sci. 20(4475)2019.PubMed/NCBI View Article : Google Scholar | |
Peng B, Hou S, Shi Q and Jia L: The relationship between cartilage end-plate calcification and disc degeneration: An experimental study. Chin Med J (Engl). 114:308–312. 2001.PubMed/NCBI | |
Bian Q, Liang QQ, Wan C, Hou W, Li CG, Zhao YJ, Lu S, Shi Q and Wang YJ: Prolonged upright posture induces calcified hypertrophy in the cartilage end plate in rat lumbar spine. Spine (Phila Pa 1976). 36:2011–2020. 2011.PubMed/NCBI View Article : Google Scholar | |
Feng C, Liu M, Fan X, Yang M, Liu H and Zhou Y: Intermittent cyclic mechanical tension altered the microRNA expression profile of human cartilage endplate chondrocytes. Mol Med Rep. 17:5238–5246. 2018.PubMed/NCBI View Article : Google Scholar | |
Chen H, Wang J, Hu B, Wu X, Chen Y, Li R and Yuan W: MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2. Mol Cell Biochem. 406:21–30. 2015.PubMed/NCBI View Article : Google Scholar | |
Onodera K, Takahashi I, Sasano Y, Bae JW and Mitani H, Kagayama M and Mitani H: Stepwise mechanical stretching inhibits chondrogenesis through cell-matrix adhesion mediated by integrins in embryonic rat limb-bud mesenchymal cells. Eur J Cell Biol. 84:45–58. 2005.PubMed/NCBI View Article : Google Scholar | |
Bleuel J, Zaucke F, Brüggemann GP and Niehoff A: Effects of cyclic tensile strain on chondrocyte metabolism: A systematic review. PLoS One. 10(e0119816)2015.PubMed/NCBI View Article : Google Scholar | |
Yuan W, Che W, Jiang YQ, Yuan FL, Wang HR, Zheng GL, Li XL and Dong J: Establishment of intervertebral disc degeneration model induced by ischemic sub-endplate in rat tail. Spine J. 15:1050–1059. 2015.PubMed/NCBI View Article : Google Scholar | |
Xiao L, Xu S, Xu Y, Liu C, Yang B, Wang J and Xu H: TGF-β/SMAD signaling inhibits intermittent cyclic mechanical tension-induced degeneration of endplate chondrocytes by regulating the miR-455-5p/RUNX2 axis. J Cell Biochem. 119:10415–10425. 2018.PubMed/NCBI View Article : Google Scholar | |
Liu MH, Sun C, Yao Y, Fan X, Liu H, Cui YH, Bian XW, Huang B and Zhou Y: Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression. Sci Rep. 6(25401)2016.PubMed/NCBI View Article : Google Scholar | |
Zhang F, Zhao X, Shen H and Zhang C: Molecular mechanisms of cell death in intervertebral disc degeneration (Review). Int J Mol Med. 37:1439–1448. 2016.PubMed/NCBI View Article : Google Scholar | |
Chen WK, Yu XH, Yang W, Wang C, He WS, Yan YG, Zhang J and Wang WJ: lncRNAs: Novel players in intervertebral disc degeneration and osteoarthritis. Cell Prolif. 50(e12313)2017.PubMed/NCBI View Article : Google Scholar | |
Sheng B, Yuan Y, Liu X, Zhang Y, Liu H, Shen X, Liu B and Chang L: Protective effect of estrogen against intervertebral disc degeneration is attenuated by miR-221 through targeting estrogen receptor α. Acta Biochim Biophys Sin (Shanghai). 50:345–354. 2018.PubMed/NCBI View Article : Google Scholar | |
Chen Y, Chen Q, Zhong M, Xu C, Wu Y and Chen R: miR-637 inhibits osteogenic differentiation of human intervertebral disc cartilage endplate stem cells by targeting WNT5A. J Invest Surg. 35:1313–1321. 2022.PubMed/NCBI View Article : Google Scholar | |
Chen D and Jiang X: Exosomes-derived miR-125-5p from cartilage endplate stem cells regulates autophagy and ECM metabolism in nucleus pulposus by targeting SUV38H1. Exp Cell Res. 414(113066)2022.PubMed/NCBI View Article : Google Scholar | |
Wang B, Ji D, Xing W, Li F, Huang Z, Zheng W, Xue J, Zhu Y and Yang X: miR-142-3p and HMGB1 are negatively regulated in proliferation, apoptosis, migration, and autophagy of cartilage endplate cells. Cartilage. 13 (2_suppl):592S–603S. 2021.PubMed/NCBI View Article : Google Scholar | |
Jarroux J, Morillon A and Pinskaya M: History, discovery, and classification of lncRNAs. Adv Exp Med Biol. 1008:1–46. 2017.PubMed/NCBI View Article : Google Scholar | |
Qian X, Zhao J, Yeung PY, Zhang QC and Kwok CK: Revealing lncRNA structures and interactions by sequencing-based approaches. Trends Biochem Sci. 44:33–52. 2019.PubMed/NCBI View Article : Google Scholar | |
Khan S, Masood M, Gaur H, Ahmad S and Syed MA: Long non-coding RNA: An immune cells perspective. Life Sci. 271(119152)2021.PubMed/NCBI View Article : Google Scholar | |
Bridges MC, Daulagala AC and Kourtidis A: LNCcation: lncRNA localization and function. J Cell Biol. 220(e202009045)2021.PubMed/NCBI View Article : Google Scholar | |
Huang H, Xing D, Zhang Q, Li H and Lin J, He Z and Lin J: LncRNAs as a new regulator of chronic musculoskeletal disorder. Cell Prolif. 54(e13113)2021.PubMed/NCBI View Article : Google Scholar | |
Liu X, Li W, Jiang L, Lü Z, Liu M, Gong L, Liu B, Liu L and Yin X: Immunity-associated long non-coding RNA and expression in response to bacterial infection in large yellow croaker (Larimichthys crocea). Fish Shellfish Immunol. 94:634–642. 2019.PubMed/NCBI View Article : Google Scholar | |
Li Z, Li X, Chen C, Li S, Shen J, Tse G, Chan MTV and Wu WKK: Long non-coding RNAs in nucleus pulposus cell function and intervertebral disc degeneration. Cell Prolif. 51(e12483)2018.PubMed/NCBI View Article : Google Scholar | |
Zhu J, Zhang X, Gao W, Hu H, Wang X and Hao D: lncRNA/circRNA-miRNA-mRNA ceRNA network in lumbar intervertebral disc degeneration. Mol Med Rep. 20:3160–3174. 2019.PubMed/NCBI View Article : Google Scholar | |
Wan ZY, Song F, Sun Z, Chen YF, Zhang WL, Samartzis D, Ma CJ, Che L, Liu X, Ali MA, et al: Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: A microarray related study. Arthritis Res Ther. 16(465)2014.PubMed/NCBI View Article : Google Scholar | |
Kitagawa M, Kitagawa K, Kotake Y, Niida H and Ohhata T: Cell cycle regulation by long non-coding RNAs. Cell Mol Life Sci. 70:4785–4794. 2013.PubMed/NCBI View Article : Google Scholar | |
Solé C, Nadal-Ribelles M, de Nadal E and Posas F: A novel role for lncRNAs in cell cycle control during stress adaptation. Curr Genet. 61:299–308. 2015.PubMed/NCBI View Article : Google Scholar | |
Guiducci G and Stojic L: Long Noncoding RNAs at the crossroads of cell cycle and genome integrity. Trends Genet. 37:528–546. 2021.PubMed/NCBI View Article : Google Scholar | |
Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014.PubMed/NCBI View Article : Google Scholar | |
Ballarino M, Morlando M, Fatica A and Bozzoni I: Non-coding RNAs in muscle differentiation and musculoskeletal disease. J Clin Invest. 126:2021–2030. 2016.PubMed/NCBI View Article : Google Scholar | |
Delás MJ, Sabin LR, Dolzhenko E, Knott SR, Munera Maravilla E, Jackson BT, Wild SA, Kovacevic T, Stork EM, Zhou M, et al: lncRNA requirements for mouse acute myeloid leukemia and normal differentiation. Elife. 6(e25607)2017.PubMed/NCBI View Article : Google Scholar | |
Deniz E and Erman B: Long noncoding RNA (lincRNA), a new paradigm in gene expression control. Funct Integr Genomics. 17:135–143. 2017.PubMed/NCBI View Article : Google Scholar | |
Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, Mitra S, Mohammed A, James AR, Hoberg E, et al: MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat Commun. 6(7743)2015.PubMed/NCBI View Article : Google Scholar | |
Mi D, Cai C, Zhou B, Liu X, Ma P, Shen S, Lu W and Huang W: Long non-coding RNA FAF1 promotes intervertebral disc degeneration by targeting the Erk signaling pathway. Mol Med Rep. 17:3158–3163. 2018.PubMed/NCBI View Article : Google Scholar | |
Yuan J, Jia J, Wu T, Liu X, Hu S, Zhang J, Ding R, Pang C and Cheng X: Comprehensive evaluation of differential long non-coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra. Exp Ther Med. 20(260)2020.PubMed/NCBI View Article : Google Scholar | |
Li B, Balasubramanian K, Krakow D and Cohn DH: Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network. BMC Genomics. 18(983)2017.PubMed/NCBI View Article : Google Scholar | |
Gu W, Zhu Q, Gao X and Brown MD: Simulation of the progression of intervertebral disc degeneration due to decreased nutritional supply. Spine (Phila Pa 1976). 39:E1411–E1417. 2014.PubMed/NCBI View Article : Google Scholar | |
Fields AJ, Berg-Johansen B, Metz LN, Miller S, La B, Liebenberg EC, Coughlin DG, Graham JL, Stanhope KL, Havel PJ and Lotz JC: Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes. J Orthop Res. 33:738–746. 2015.PubMed/NCBI View Article : Google Scholar | |
Agius R, Galea R and Fava S: Bone mineral density and intervertebral disc height in type 2 diabetes. J Diabetes Complications. 30:644–650. 2016.PubMed/NCBI View Article : Google Scholar | |
Jiang Z, Lu W, Zeng Q, Li D, Ding L and Wu J: High glucose-induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells. J Orthop Res. 36:2476–2483. 2018.PubMed/NCBI View Article : Google Scholar | |
Li X, Wu FR, Xu RS, Hu W, Jiang DL, Ji C, Chen FH and Yuan FL: Acid-sensing ion channel 1a-mediated calcium influx regulates apoptosis of endplate chondrocytes in intervertebral discs. Expert Opin Ther Targets. 18:1–14. 2014.PubMed/NCBI View Article : Google Scholar | |
Yuan FL, Wang HR, Zhao MD, Yuan W, Cao L, Duan PG, Jiang YQ, Li XL and Dong J: Ovarian cancer G protein-coupled receptor 1 is involved in acid-induced apoptosis of endplate chondrocytes in intervertebral discs. J Bone Miner Res. 29:67–77. 2014.PubMed/NCBI View Article : Google Scholar | |
Jiang Z, Zeng Q, Li D, Ding L, Lu W, Bian M and Wu J: Long non-coding RNA MALAT1 promotes high glucose-induced rat cartilage endplate cell apoptosis via the p38/MAPK signalling pathway. Mol Med Rep. 21:2220–2226. 2020.PubMed/NCBI View Article : Google Scholar | |
Sanger HL, Klotz G, Riesner D, Gross HJ and Kleinschmidt AK: Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA. 73:3852–3856. 1976.PubMed/NCBI View Article : Google Scholar | |
Hsu MT and Coca-Prados M: Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature. 280:339–340. 1979.PubMed/NCBI View Article : Google Scholar | |
Capel B, Swain A, Nicolis S, Hacker A, Walter M, Koopman P, Goodfellow P and Lovell-Badge R: Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell. 73:1019–1030. 1993.PubMed/NCBI View Article : Google Scholar | |
Grabowski PJ, Zaug AJ and Cech TR: The intervening sequence of the ribosomal RNA precursor is converted to a circular RNA in isolated nuclei of Tetrahymena. Cell. 23:467–476. 1981.PubMed/NCBI View Article : Google Scholar | |
Ford E and Ares M Jr: Synthesis of circular RNA in bacteria and yeast using RNA cyclase ribozymes derived from a group I intron of phage T4. Proc Natl Acad Sci USA. 91:3117–3121. 1994.PubMed/NCBI View Article : Google Scholar | |
Kos A, Dijkema R, Arnberg AC, van der Meide PH and Schellekens H: The hepatitis delta (delta) virus possesses a circular RNA. Nature. 323:558–560. 1986.PubMed/NCBI View Article : Google Scholar | |
Chen LL: The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat Rev Mol Cell Biol. 21:475–490. 2020.PubMed/NCBI View Article : Google Scholar | |
Xiao MS, Ai Y and Wilusz JE: Biogenesis and functions of circular RNAs come into focus. Trends Cell Biol. 30:226–240. 2020.PubMed/NCBI View Article : Google Scholar | |
Jeck WR and Sharpless NE: Detecting and characterizing circular RNAs. Nat Biotechnol. 32:453–461. 2014.PubMed/NCBI View Article : Google Scholar | |
O'Conor CJ, Case N and Guilak F: Mechanical regulation of chondrogenesis. Stem Cell Res Ther. 4(61)2013.PubMed/NCBI View Article : Google Scholar | |
Xia DD, Lin SL, Wang XY, Wang YL, Xu HM, Zhou F and Tan J: Effects of shear force on intervertebral disc: An in vivo rabbit study. Eur Spine J. 24:1711–1719. 2015.PubMed/NCBI View Article : Google Scholar | |
Xiao L, Ding B, Xu S, Gao J, Yang B, Wang J and Xu H: circRNA_0058097 promotes tension-induced degeneration of endplate chondrocytes by regulating HDAC4 expression through sponge adsorption of miR-365a-5p. J Cell Biochem. 121:418–429. 2020.PubMed/NCBI View Article : Google Scholar | |
Li X, Yang L and Chen LL: The biogenesis, functions, and challenges of circular RNAs. Mol Cell. 71:428–442. 2018.PubMed/NCBI View Article : Google Scholar | |
Ren S, Lin P, Wang J, Yu H, Lv T, Sun L and Du G: Circular RNAs: Promising molecular biomarkers of human aging-related diseases via functioning as an miRNA Sponge. Mol Ther Methods Clin Dev. 18:215–229. 2020.PubMed/NCBI View Article : Google Scholar | |
Xu D, Ma X, Sun C, Han J, Zhou C, Wong SH, Chan MTV and Wu WKK: Circular RNAs in intervertebral disc degeneration: An updated review. Front Mol Biosci. 8(781424)2022.PubMed/NCBI View Article : Google Scholar | |
Zhang J, Hu S, Ding R, Yuan J, Jia J, Wu T and Cheng X: CircSNHG5 Sponges Mir-495-3p and Modulates CITED2 to protect cartilage endplate from degradation. Front Cell Dev Biol. 9(668715)2021.PubMed/NCBI View Article : Google Scholar | |
Larsson ME and Nordholm LA: Responsibility for managing musculoskeletal disorders-a cross-sectional postal survey of attitudes. BMC Musculoskelet Disord. 9(110)2008.PubMed/NCBI View Article : Google Scholar | |
Hu B, Xiao L, Wang C, Liu C, Zhang Y, Ding B, Gao D, Lu Y and Xu H: Circ_0022382 ameliorated intervertebral disc degeneration by regulating TGF-β3 expression through sponge adsorption of miR-4726-5p. Bone. 154(116185)2022.PubMed/NCBI View Article : Google Scholar | |
Zhang H, Wu S, Chen W, Hu Y, Geng Z and Su J: Bone/cartilage targeted hydrogel: Strategies and applications. Bioact Mater. 23:156–169. 2022.PubMed/NCBI View Article : Google Scholar | |
Guo J, Wang F, Hu Y, Luo Y, Wei Y, Xu K, Zhang H, Liu H, Bo L, Lv S, et al: Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases. Cell Rep Med. 4(100881)2023.PubMed/NCBI View Article : Google Scholar | |
Ji ML, Jiang H, Zhang XJ, Shi PL, Li C, Wu H, Wu XT, Wang YT, Wang C and Lu J: Preclinical development of a microRNA-based therapy for intervertebral disc degeneration. Nat Commun. 9(5051)2018.PubMed/NCBI View Article : Google Scholar | |
Hu Y, Li X, Zhang Q, Gu Z, Luo Y, Guo J, Wang X, Jing Y, Chen X and Su J: Exosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss. Bioact Mater. 6:2905–2913. 2021.PubMed/NCBI View Article : Google Scholar | |
Wang Y, Chu X and Wang B: Recombinant adeno-associated virus-based gene therapy combined with tissue engineering for musculoskeletal regenerative medicine. Biomater Transl. 2:19–29. 2021.PubMed/NCBI View Article : Google Scholar | |
Ahn J, Park EM, Kim BJ, Kim JS, Choi B, Lee SH and Han I: Transplantation of human Wharton's jelly-derived mesenchymal stem cells highly expressing TGFβ receptors in a rabbit model of disc degeneration. Stem Cell Res Ther. 6(190)2015.PubMed/NCBI View Article : Google Scholar |