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Varghese B, Babu S, Jala A, Das P, Raju R, Borkar RM, Adela R. Integrative Placental Multi-Omics Analysis Reveals Perturbed Pathways and Potential Prognostic Biomarkers in Gestational Hypertension. Arch Med Res 2024; 55:102909. [PMID: 37984232 DOI: 10.1016/j.arcmed.2023.102909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 09/26/2023] [Accepted: 10/27/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND Gestational hypertension (GH) is a severe complication that occurs after 20 weeks of pregnancy; however, its molecular mechanisms are not yet fully understood. OBJECTIVE Through this case-control discovery phase study, we aimed to find disease-specific candidate placental microRNAs (miRNAs) and metabolite markers for differentiating GH by integrating next-generation sequencing and metabolomics multi-omics analysis of placenta. Using small RNA sequencing and metabolomics of placental tissues of healthy pregnant (HP, n = 24) and GH subjects (n = 20), the transcriptome and metabolome were characterized in both groups. RESULTS The study identified a total of 44 downregulated placental miRNAs which includes three novel, three mature and 38 precursor miRNAs. Six miRNAs including three mature (hsa-miR-181a-5p, hsa-miR-498-5p, and hsa-miR-26b-5p) and three novel (NC_000016.10_1061, NC_000005.10_475, and NC_000001.11_53) were considered for final target prediction and functional annotation. Integrative analysis of differentially expressed miRNAs and metabolites yielded five pathways such as purine, glutathione, glycerophospholipid, inositol phosphate and β-alanine to be significantly perturbed in GH. We present fourteen genes (LPCAT1, LPCAT2, DGKH, PISD, GPAT2, PTEN, SACM1L, PGM2, AMPD3, AK7, AK3, CNDP1, IDH2, and ODC1) and eight metabolites (xanthosine, xanthine, spermine, glycine, CDP-Choline, glyceraldehyde 3-phosphate, β-alanine, and histidine) with potential to distinguish GH and HP. CONCLUSION The differential expression of miRNAs, their target genes, altered metabolites and metabolic pathways in GH patients were identified for the first time in our study. Further, the altered miRNAs and metabolites were integrated to build their inter-connectivity network. The findings obtained from our study may be used as a valuable source to further unravel the molecular pathways associated with GH and also for the evaluation of prognostic markers.
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Affiliation(s)
- Bincy Varghese
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India
| | - Sreeranjini Babu
- Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India; Centre for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India
| | - Aishwarya Jala
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India
| | - Panchanan Das
- Department of Obstetrics and Gynecology, Gauhati Medical College, Guwahati, Assam, India
| | - Rajesh Raju
- Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India
| | - Roshan M Borkar
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India
| | - Ramu Adela
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India.
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Wang D, Fang Y, Lin L, Long W, Wang L, Yu L, Deng H, Wang D. Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11. BMC Musculoskelet Disord 2023; 24:862. [PMID: 37932746 PMCID: PMC10629093 DOI: 10.1186/s12891-023-07003-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 10/31/2023] [Indexed: 11/08/2023] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a common disease with a complex pathology. This study aimed to investigate the correlation between the aberrant upregulation of miR-181b and ferroptosis in chondrocytes during the progression of OA. METHODS An OA cell model was constructed with erastin. Ferrostatin-1 (Fer), bioinformatics, and dual-luciferase activity reports were used to investigate the effect of miR-181b on OA. Finally, a rat model of OA was induced by monosodium iodoacetate to verify that miR-181b inhibits SLC7A11 gene expression and increases ferroptosis. RESULTS The results showed that Fer could effectively reverse the erastin-induced inhibition of human chondrocyte viability, increase the level of collagenous proteins in human chondrocytes, and inhibit oxidative stress and ferroptosis. MiR-181b is abnormally elevated in OA cell models. Transfection of a miR-181b inhibitor could increase the expression levels of the ferroptosis-related proteins solute carrier family 7 members 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thereby inhibiting the occurrence of ferroptosis in chondrocytes. In addition, hsa-miR-181b-5p and SLC7A11 have a targeted regulatory effect. Transfection of SLC7A11 siRNA effectively abrogated the increase in chondrocyte viability induced by the miR-181 inhibitor and increased ferroptosis. Finally, miR-181b was shown to exacerbate OA disease progression by inhibiting SLC7A11 gene expression and increasing ferroptosis in a rat OA model. CONCLUSIONS Elevating miR-181b may mediate chondrocyte ferroptosis by targeting SLC7A11 in OA.
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Affiliation(s)
- Dexin Wang
- Department of Orthopaedics, Haishu Branch, Ningbo First Hospital, Ningbo, 315153, China
| | - Yu Fang
- Department of Orthopaedics, Haishu Branch, Ningbo First Hospital, Ningbo, 315153, China
| | - Liang Lin
- Department of Orthopaedics, Haishu Branch, Ningbo First Hospital, Ningbo, 315153, China
| | - Wensuo Long
- Department of Orthopaedics, Haishu Branch, Ningbo First Hospital, Ningbo, 315153, China
| | - Lei Wang
- Department of Orthopaedics, Haishu Branch, Ningbo First Hospital, Ningbo, 315153, China
| | - Liwei Yu
- Department of Orthopaedics, Haishu Branch, Ningbo First Hospital, Ningbo, 315153, China
| | - Huaiming Deng
- Department of Orthopaedics, Haishu Branch, Ningbo First Hospital, Ningbo, 315153, China
| | - Dan Wang
- Department of Pharmacology, Medical College of Dalian University, Dalian, 116622, China.
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Yoon J, Kaya S, Matsumae G, Dole N, Alliston T. miR181a/b-1 controls osteocyte metabolism and mechanical properties independently of bone morphology. Bone 2023; 175:116836. [PMID: 37414200 PMCID: PMC11156520 DOI: 10.1016/j.bone.2023.116836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/30/2023] [Accepted: 07/01/2023] [Indexed: 07/08/2023]
Abstract
Bone derives its ability to resist fracture from bone mass and quality concurrently; however, many questions about the molecular mechanisms controlling bone quality remain unanswered, limiting the development of diagnostics and therapeutics. Despite the increasing evidence on the importance of miR181a/b-1 in bone homeostasis and disease, whether and how osteocyte-intrinsic miR181a/b-1 controls bone quality remains elusive. Osteocyte-intrinsic deletion of miR181a/b-1 in osteocytes in vivo resulted in compromised overall bone mechanical behavior in both sexes, although the parameters affected by miR181a/b-1 varied distinctly based on sex. Furthermore, impaired fracture resistance in both sexes was unexplained by cortical bone morphology, which was altered in female mice and intact in male mice with miR181a/b-1-deficient osteocytes. The role of miR181a/b-1 in the regulation of osteocyte metabolism was apparent in bioenergetic testing of miR181a/b-1-deficient OCY454 osteocyte-like cells and transcriptomic analysis of cortical bone from mice with osteocyte-intrinsic ablation of miR181a/b-1. Altogether, this study demonstrates the control of osteocyte bioenergetics and the sexually dimorphic regulation of cortical bone morphology and mechanical properties by miR181a/b-1, hinting at the role of osteocyte metabolism in the regulation of mechanical behavior.
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Affiliation(s)
- Jihee Yoon
- Department of Orthopaedic Surgery, University of California San Francisco, California, USA; Oral and Craniofacial Sciences Program, School of Dentistry, University of California San Francisco, California, USA
| | - Serra Kaya
- Department of Orthopaedic Surgery, University of California San Francisco, California, USA
| | - Gen Matsumae
- Department of Orthopaedic Surgery, University of California San Francisco, California, USA
| | - Neha Dole
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, AR, USA
| | - Tamara Alliston
- Department of Orthopaedic Surgery, University of California San Francisco, California, USA; Oral and Craniofacial Sciences Program, School of Dentistry, University of California San Francisco, California, USA.
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Arias C, Salazar LA. Ethanolic Extract of Propolis Modulates Autophagy-Related microRNAs in Osteoarthritic Chondrocytes. Int J Mol Sci 2023; 24:14767. [PMID: 37834215 PMCID: PMC10573165 DOI: 10.3390/ijms241914767] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/17/2023] [Accepted: 09/25/2023] [Indexed: 10/15/2023] Open
Abstract
Osteoarthritis is a multifactorial joint disease characterized by degeneration, and aging stands as a significant risk factor. Autophagy, a crucial cellular homeostasis mechanism, is influenced by aging and closely linked to cartilage health. This correlation between autophagy, cell death, and OA underscores its relevance in disease progression. MicroRNAs have emerged as autophagy regulators, with miRNA-based interventions showing promise in preclinical models. Remarkably, the ethanolic extract of propolis exhibits positive effects on autophagy-related proteins and healthy cartilage markers in an in vitro osteoarthritis model. The aim of this brief report was to evaluate through in silico analysis and postulate five microRNAs that could regulate autophagy proteins (AKT1, ATG5, and LC3) and assess whether the ethanolic extract of propolis could regulate the expression of these microRNAs. Among the examined miRNAs (miR-19a, miR-125b, miR-181a, miR-185, and miR-335), the ethanolic extract of propolis induced significant changes in four of them. Specifically, miR-125b responded to EEP by counteracting IL-1β-induced effects, while miR-181a, miR-185, and miR-335 exhibited distinct patterns of expression under EEP treatment. These findings unveil a potential link between miRNAs, EEP, and autophagy modulation in OA, offering promising therapeutic insights. Nevertheless, further validation and clinical translation are warranted to substantiate these promising observations.
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Affiliation(s)
- Consuelo Arias
- Escuela de Kinesiología, Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Santiago 8380000, Chile
| | - Luis A Salazar
- Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile
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Zhao P, Ma G, Ma L. miR-181a-5p targets DDX3X to inhibit the progression of osteoarthritis via NF-ΚB signaling pathway. J Orthop Surg Res 2023; 18:606. [PMID: 37587519 PMCID: PMC10433630 DOI: 10.1186/s13018-023-04073-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 08/03/2023] [Indexed: 08/18/2023] Open
Abstract
Osteoarthritis (OA) is the most common age-related joint disease, characterized by chronic inflammation, progressive articular cartilage destruction and subchondral osteosclerosis. More and more evidence showed that microRNAs (miRNAs) play a key role in various diseases, but the specific mechanism of miRNAs in OA is not clear. The purpose of this study was to investigate the expression level and role of miR-181a-5p in OA and its related mechanism. Here we identified the key gene DEAD-box RNA helicase 3X (DDX3X) in the OA dataset by bioinformatics analysis. At the same time, miRNAs targeting DDX3X were screened, and miR-181a-5p was selected as the next research object. Then we used different concentrations of interleukin-1 beta (IL-1β)-induced in vitro model of arthritis, and found that IL-1β can stimulate cells to release nitric oxide. The expression levels of miR-181a-5p and DDX3X in mouse chondrocyte cell line ATDC5 induced by IL-1β at a concentration of 10ug/mL were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). IL-1β induced a decrease in the expression of miR-181a-5p and an increase in the expression of DDX3X in ATDC5 cells. mimic miR-181a-5p or inhibitor miR-181a-5p were transfected into ATDC5 cells, and the levels of inflammatory mediators in the cells were detected by enzyme-linked immunosorbent assay, and the results showed that miR-181a-5p could reduce the release of tumor necrosis factor-α, IL-1β, IL-6 and inducible nitric oxide nitric oxide synthase in a cellular model of arthritis. Luciferase reporter assays confirmed that the miR-181a-5p binding site was in the DDX3X gene 3'-untranslated region (3'-UTR), and DDX3X was negatively regulated by miR-181a-5p. Rescue assays confirmed that miR-181a-5p reduced the expression of DDX3X by targeting the 3'-UTR region of DDX3X, thereby reducing the release of inflammatory factors. Finally, in this paper, western blot was used to detect the mechanism of miR-181a-5p regulating OA. The results showed that interfering with the expression of miR-181a-5p could up-regulate the expression of DDX3X protein, increase the expression of nuclear factor- kappaB (NF-κB) related proteins, and reduce the inflammatory response of OA, thereby increasing the secretion of the matrix proteinases MMP-3 and MMP-13. Taken together, the results of the study suggested that miR-181a-5p may be a promising therapeutic target for the treatment of human OA.
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Affiliation(s)
- Peng Zhao
- Department of Rheumatology Immunology, 3201 Hospital, 783 Tianhan Avenue, Hantai District, Hanzhong, 723000, China.
| | - Guobin Ma
- Department of Rheumatology Immunology, 3201 Hospital, 783 Tianhan Avenue, Hantai District, Hanzhong, 723000, China
| | - Lintong Ma
- Department of Hematology, 3201 Hospital, Hanzhong, China
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Bell-Hensley A, Das S, McAlinden A. The miR-181 family: Wide-ranging pathophysiological effects on cell fate and function. J Cell Physiol 2023; 238:698-713. [PMID: 36780342 PMCID: PMC10121854 DOI: 10.1002/jcp.30969] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/19/2023] [Accepted: 01/23/2023] [Indexed: 02/14/2023]
Abstract
MicroRNAs (miRNAs) are epigenetic regulators that can target and inhibit translation of multiple mRNAs within a given cell type. As such, a number of different pathways and networks may be modulated as a result. In fact, miRNAs are known to regulate many cellular processes including differentiation, proliferation, inflammation, and metabolism. This review focuses on the miR-181 family and provides information from the published literature on the role of miR-181 homologs in regulating a range of activities in different cell types and tissues. Of note, we have not included details on miR-181 expression and function in the context of cancer since this is a broad topic area requiring independent review. Instead, we have focused on describing the function and mechanism of miR-181 family members on differentiation toward a number of cell lineages in various non-neoplastic conditions (e.g., immune/hematopoietic cells, osteoblasts, osteoclasts, chondrocytes, adipocytes). We have also provided information on how modulation of miR-181 homologs can have positive effects on disease states such as cardiac abnormalities, pulmonary arterial hypertension, thrombosis, osteoarthritis, and vascular inflammation. In this context, we have used some examples of FDA-approved drugs that modulate miR-181 expression. We conclude by discussing some common mechanisms by which miR-181 homologs appear to regulate a number of different cellular processes and how targeting specific miR-181 family members may lead to attractive therapeutic approaches to treat a number of human disease or repair conditions, including those associated with the aging process.
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Affiliation(s)
- Austin Bell-Hensley
- Department of Biomedical Engineering, Washington University School of Medicine, St Louis, Missouri
| | - Samarjit Das
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Audrey McAlinden
- Department of Orthopaedic Surgery Washington University School of Medicine, St Louis, Missouri
- Department of Cell Biology & Physiology, Washington University School of Medicine, St Louis, Missouri, USA
- Shriners Hospital for Children – St Louis, Missouri
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Ibáñez-Cabellos JS, Pallardó FV, García-Giménez JL, Seco-Cervera M. Oxidative Stress and Epigenetics: miRNA Involvement in Rare Autoimmune Diseases. Antioxidants (Basel) 2023; 12:antiox12040800. [PMID: 37107175 PMCID: PMC10135388 DOI: 10.3390/antiox12040800] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/16/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Autoimmune diseases (ADs) such as Sjögren’s syndrome, Kawasaki disease, and systemic sclerosis are characterized by chronic inflammation, oxidative stress, and autoantibodies, which cause joint tissue damage, vascular injury, fibrosis, and debilitation. Epigenetics participate in immune cell proliferation and differentiation, which regulates the development and function of the immune system, and ultimately interacts with other tissues. Indeed, overlapping of certain clinical features between ADs indicate that numerous immunologic-related mechanisms may directly participate in the onset and progression of these diseases. Despite the increasing number of studies that have attempted to elucidate the relationship between miRNAs and oxidative stress, autoimmune disorders and oxidative stress, and inflammation and miRNAs, an overall picture of the complex regulation of these three actors in the pathogenesis of ADs has yet to be formed. This review aims to shed light from a critical perspective on the key AD-related mechanisms by explaining the intricate regulatory ROS/miRNA/inflammation axis and the phenotypic features of these rare autoimmune diseases. The inflamma-miRs miR-155 and miR-146, and the redox-sensitive miR miR-223 have relevant roles in the inflammatory response and antioxidant system regulation of these diseases. ADs are characterized by clinical heterogeneity, which impedes early diagnosis and effective personalized treatment. Redox-sensitive miRNAs and inflamma-miRs can help improve personalized medicine in these complex and heterogeneous diseases.
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Affiliation(s)
| | - Federico V. Pallardó
- U733, Centre for Biomedical Network Research on Rare Diseases (CIBERER-ISCIII), 28029 Madrid, Spain
- Mixed Unit for Rare Diseases INCLIVA-CIPF, INCLIVA Health Research Institute, 46010 Valencia, Spain
- Department Physiology, Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain
- Correspondence: (F.V.P.); (J.L.G.-G.); (M.S.-C.); Tel.: +34-963-864-646 (F.V.P.)
| | - José Luis García-Giménez
- U733, Centre for Biomedical Network Research on Rare Diseases (CIBERER-ISCIII), 28029 Madrid, Spain
- Mixed Unit for Rare Diseases INCLIVA-CIPF, INCLIVA Health Research Institute, 46010 Valencia, Spain
- Department Physiology, Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain
- Correspondence: (F.V.P.); (J.L.G.-G.); (M.S.-C.); Tel.: +34-963-864-646 (F.V.P.)
| | - Marta Seco-Cervera
- Hospital Dr. Peset, Fundación para la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, FISABIO, 46010 Valencia, Spain
- Correspondence: (F.V.P.); (J.L.G.-G.); (M.S.-C.); Tel.: +34-963-864-646 (F.V.P.)
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Brophy RH, Cai L, Zhang Q, Townsend RR, Rai MF. Proteomic Profile Analysis of Synovial Fluid in Patients With Anterior Cruciate Ligament Tears. Am J Sports Med 2022; 50:2935-2943. [PMID: 35969389 DOI: 10.1177/03635465221112652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Anterior cruciate ligament (ACL) tears are associated with posttraumatic osteoarthritis, but the early biological changes that initiate joint degeneration after this injury are not well characterized. ACL tears typically result in effusion in the knee, which may provide insight into the initial response of the joint to injuries. HYPOTHESIS Patient- and injury-specific factors are associated with the proteomics of synovial fluid in knees with ACL tears. STUDY DESIGN Descriptive laboratory study. METHODS Synovial fluid was collected from 105 patients (38 male, 67 female) with an acute traumatic ACL tear. Patient- and injury-specific factors such as age, sex, body mass index, time from injury, presence/absence of concomitant meniscal tears, and location of concomitant bone bruises (if present) were recorded. The protein concentration of synovial fluid was measured, followed by benchmarking of samples for multi-affinity high-abundance protein depletion. An isotropically labeled high-resolution nano-liquid chromatography with tandem mass spectrometry-based proteomic approach was used to determine the synovial fluid protein profile. Data were processed, quality controlled, and analyzed computationally for each patient and injury factor. RESULTS The proteomics of synovial fluid from ACL tears was associated with patient sex, injury pattern, and location of bone bruises but not with patient age, body mass index, or time from injury. Knees with an isolated ACL tear had higher glutathione peroxidase 1 (GPX1) and plastin 3 levels than knees with an ACL tear and meniscal tear. A bone bruise on the lateral femoral condyle was associated with elevated leptin and glucose-6-phosphate dehydrogenase (G6PD) levels. A bone bruise on the lateral tibial plateau was associated with decreased GPX1 levels. Male patients had higher matrix metalloproteinase 9 and lower G6PD levels than female patients. CONCLUSION Patient sex, injury pattern, and bone bruise location were important determinants of the proteomic profile of effusion resulting from ACL tears. CLINICAL RELEVANCE Longitudinal follow-ups to see if and how proteomic differences relate to clinical outcomes and mechanistic studies to assess the role that specific proteins play in the joint are warranted. Ultimately, these investigations could lead to better approaches to predict clinical outcomes and identify possible interventions to optimize outcomes in these patients.
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Affiliation(s)
- Robert H Brophy
- Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, Missouri, USA
| | - Lei Cai
- Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, Missouri, USA
| | - Qiang Zhang
- Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
| | - R Reid Townsend
- Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
| | - Muhammad Farooq Rai
- Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, Missouri, USA.,Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri, USA
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Shu X, Chen XX, Kang XD, Ran M, Wang YL, Zhao ZK, Li CX. Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis. World J Clin Cases 2022; 10:5965-5983. [PMID: 35949853 PMCID: PMC9254198 DOI: 10.12998/wjcc.v10.i18.5965] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/30/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Psoriasis is a chronic inflammatory skin disease, the pathogenesis of which is more complicated and often requires long-term treatment. In particular, moderate to severe psoriasis usually requires systemic treatment. Psoriasis is also associated with many diseases, such as cardiometabolic diseases, malignant tumors, infections, and mood disorders. Psoriasis can appear at any age, and lead to a substantial burden for individuals and society. At present, psoriasis is still a treatable, but incurable, disease. Previous studies have found that microRNAs (miRNAs) play an important regulatory role in the progression of various diseases. Currently, miRNAs studies in psoriasis and dermatology are relatively new. Therefore, the identification of key miRNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis.
AIM To identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis.
METHODS The miRNA and mRNA data were obtained from the Gene Expression Omnibus database. Then, differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were screened out by limma R package. Subsequently, DEmRNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment. The “WGCNA” R package was used to analyze the co-expression network of all miRNAs. In addition, we constructed miRNA-mRNA regulatory networks based on identified hub miRNAs. Finally, in vitro validation was performed. All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital (S2021-012-01).
RESULTS A total of 639 DEmRNAs and 84 DEmiRNAs were identified. DEmRNAs screening criteria were adjusted P (adj. P) value < 0.01 and |logFoldChange| (|logFC|) > 1. DEmiRNAs screening criteria were adj. P value < 0.01 and |logFC| > 1.5. KEGG functional analysis demonstrated that DEmRNAs were significantly enriched in immune-related biological functions, for example, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. In weighted gene co-expression network analysis, turquoise module was the hub module. Moreover, 10 hub miRNAs were identified. Among these 10 hub miRNAs, only 8 hub miRNAs predicted the corresponding target mRNAs. 97 negatively regulated miRNA-mRNA pairs were involved in the miRNA-mRNA regulatory network, for example, hsa-miR-21-5p-claudin 8 (CLDN8), hsa-miR-30a-3p-interleukin-1B (IL-1B), and hsa-miR-181a-5p/hsa-miR-30c-2-3p-C-X-C motif chemokine ligand 9 (CXCL9). Real-time polymerase chain reaction results showed that IL-1B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences.
CONCLUSION The identification of potential key molecular markers and signaling pathways provides potential research directions for further understanding the molecular mechanisms of psoriasis. This may also provide new research ideas for the prevention and treatment of psoriasis in the future.
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Affiliation(s)
- Xin Shu
- Department of Dermatology, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- Chinese PLA Medical School, Beijing 100853, China
| | - Xiao-Xia Chen
- Department of Radiology, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xin-Dan Kang
- Department of Comprehensive Surgical, The Second Medical Center of Chinese PLA General Hospital, Beijing 100089, China
| | - Min Ran
- Department of Endocrine, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - You-Lin Wang
- Department of Dermatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Zhen-Kai Zhao
- Department of Dermatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Cheng-Xin Li
- Department of Dermatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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Qi H, Zhao Z, Xu L, Zhang Y, Li Y, Xiao L, Li Y, Zhao Z, Fang J. Antisense Oligonucleotide-Based Therapy on miR-181a-5p Alleviates Cartilage Degradation of Temporomandibular Joint Osteoarthritis via Promoting SIRT1. Front Pharmacol 2022; 13:898334. [PMID: 35784690 PMCID: PMC9240346 DOI: 10.3389/fphar.2022.898334] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/30/2022] [Indexed: 11/13/2022] Open
Abstract
Temporomandibular joint osteoarthritis (TMJOA) condylar cartilage degeneration and abnormal subchondral bone pathological remodeling induce pain and joint dysfunction, and cartilage degeneration is considered irreversible. Very few therapeutic approaches are administrated in practice. Nucleotides have demonstrated considerable potential as a next-generation medication, and they have been applied in several models of osteoarthritis. There is a need to establish an effective protocol for TMJOA gene therapy. In the current study unilateral anterior crossbite (UAC) surgery was used to simulate mechanical stress-induced TMJOA in mice. Degeneration of condylar cartilage and destruction of subchondral bone were observed in damaged joints, and miR-181a-5p was elevated in chondrocytes. Intra-articular injection of miR-181a-5p antisense oligonucleotide (ASO) could reduce the cartilage damage and alleviate UAC-induced TMJOA progression, but it did not restore injured subchondral bone. Mechanically, miR-181a-5p evidently targeted the 3’ untranslated region of Sirt1 directly, resulting in inhibition of silent information regulator 1 expression and promoting apoptosis by elevating p53-dependent signaling, indicating that miR181a-5p ASO promoted chondrocyte survival. The present study suggests that ASO-based gene therapy may be an effective TMJOA treatment.
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Affiliation(s)
- Hexu Qi
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhenxing Zhao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- College of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
| | - Lin Xu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yue Zhang
- Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children’s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yifei Li
- Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children’s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Li Xiao
- Department of Stomatology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yu Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhihe Zhao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jie Fang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Jie Fang,
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11
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Yuan A, Wu P, Zhong Z, He Z, Li W. Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis. J Orthop Surg Res 2022; 17:304. [PMID: 35689264 PMCID: PMC9185876 DOI: 10.1186/s13018-022-03202-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 05/25/2022] [Indexed: 11/10/2022] Open
Abstract
Objective This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism. Methods The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meniscus, followed by measurement of Gm37494, microRNA (miR)-181a-5p, GABRA1 mRNA, and the encoded GABAARα1 protein expression. Thereafter, a cellular model was induced by interleukin-1β (IL-1β) treatment in chondrocytes, followed by ectopic and silencing experiments. Chondrocyte proliferation was detected by CCK-8 and EdU assays, chondrocyte apoptosis by flow cytometry and western blot, and the levels of inflammatory factors by ELISA. The binding of Gm37494 to miR-181a-5p was evaluated by dual-luciferase reporter gene and RIP assays, and that of GABRA1 to miR-181a-5p by dual-luciferase reporter gene and RNA pull-down assays. Results OA patients and mice had decreased GABRA1 mRNA and GABAARα1 protein levels and elevated miR-181a-5p expression in cartilage tissues. Additionally, Gm37494 was poorly expressed in OA mice. Mechanistically, Gm37494 directly bound to and inversely modulated miR-181a-5p that negatively targeted GABRA1. In IL-1β-induced chondrocytes, Gm37494 overexpression enhanced cell proliferation and suppressed cell apoptosis and inflammation, whereas further miR-181a-5p up-regulation or GABRA1 silencing abolished these trends. Conclusions Conclusively, Gm37494 elevated GABRA1 expression by binding to miR-181a-5p, thus ameliorating OA-induced chondrocyte damage. Supplementary Information The online version contains supplementary material available at 10.1186/s13018-022-03202-5.
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Affiliation(s)
- Aidong Yuan
- Department of Joint and Sports Medicine, The First People's Hospital of Shaoguan City, No.3 Dongdi South Road, Zhenjiang District, Shaoguan, 512000, Guangdong, People's Republic of China.
| | - Penghuan Wu
- Department of Joint and Sports Medicine, The First People's Hospital of Shaoguan City, No.3 Dongdi South Road, Zhenjiang District, Shaoguan, 512000, Guangdong, People's Republic of China
| | - Zhinian Zhong
- Department of Joint and Sports Medicine, The First People's Hospital of Shaoguan City, No.3 Dongdi South Road, Zhenjiang District, Shaoguan, 512000, Guangdong, People's Republic of China
| | - Zhengyan He
- Department of Joint and Sports Medicine, The First People's Hospital of Shaoguan City, No.3 Dongdi South Road, Zhenjiang District, Shaoguan, 512000, Guangdong, People's Republic of China
| | - Wenhu Li
- Department of Joint and Sports Medicine, The First People's Hospital of Shaoguan City, No.3 Dongdi South Road, Zhenjiang District, Shaoguan, 512000, Guangdong, People's Republic of China
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Wei ZD, Shetty AK. Can mild cognitive impairment and Alzheimer's disease be diagnosed by monitoring a miRNA triad in the blood? Aging Cell 2022; 21:e13627. [PMID: 35537095 PMCID: PMC9197398 DOI: 10.1111/acel.13627] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/21/2022] [Accepted: 04/26/2022] [Indexed: 11/29/2022] Open
Abstract
Objectively diagnosing age‐related cognitive impairment (ACI), mild cognitive impairment (MCI), and early‐stage Alzheimer's disease (AD) is a difficult task, as most cognitive impairment is clinically established via questionnaires, history, and physical examinations. A recent study has suggested that monitoring a miRNA triad, miR‐181a‐5p, miR‐146a‐5p, and miR‐148a‐3p can identify ACI and its progression to MCI and AD (Islam et al., EMBO Mol Med. 13: e14997, 2021). This commentary deliberates findings from this article, such as elevated levels of the miRNA triad in the brain impairing neural plasticity and cognitive function, the efficiency of measuring the miRNA triad in the circulating blood diagnosing MCI and AD, and the promise for improving cognitive function in MCI and AD by inhibiting this miRNA triad. Additional studies required prior to employing this miRNA triad in clinical practice are also discussed.
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Affiliation(s)
- Zhuang‐Yao D. Wei
- Institute for Regenerative Medicine Department of Molecular and Cellular Medicine Texas A&M University Health Science Center College of Medicine College Station Texas USA
| | - Ashok K. Shetty
- Institute for Regenerative Medicine Department of Molecular and Cellular Medicine Texas A&M University Health Science Center College of Medicine College Station Texas USA
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Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Alshaer W, Hasan H, Albakri KA, Alkhafaji E, Issa NN, Al-Holy MA, Abderrahman SM, Abdallah AM, Mohamud R. Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects. Biomedicines 2022; 10:1219. [PMID: 35740242 PMCID: PMC9219990 DOI: 10.3390/biomedicines10061219] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 02/07/2023] Open
Abstract
Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant's early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.
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Affiliation(s)
- Ma’mon M. Hatmal
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Mohammad A. I. Al-Hatamleh
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
| | - Amin N. Olaimat
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Walhan Alshaer
- Cell Therapy Center (CTC), The University of Jordan, Amman 11942, Jordan;
| | - Hanan Hasan
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan;
| | - Khaled A. Albakri
- Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Enas Alkhafaji
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan;
| | - Nada N. Issa
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Murad A. Al-Holy
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Salim M. Abderrahman
- Department of Biology and Biotechnology, Faculty of Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Atiyeh M. Abdallah
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar;
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
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Li Z, Zhu Z, Liu Y, Liu Y, Zhao H. Function and regulation of GPX4 in the development and progression of fibrotic disease. J Cell Physiol 2022; 237:2808-2824. [PMID: 35605092 DOI: 10.1002/jcp.30780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 04/21/2022] [Accepted: 04/26/2022] [Indexed: 02/06/2023]
Abstract
Fibrosis is a common feature of fibrotic diseases that poses a serious threat to global health due to high morbidity and mortality in developing countries. There exist some chemical compounds and biomolecules associated with the development of fibrosis, including cytokines, hormones, and enzymes. Among them, glutathione peroxidase 4 (GPX4), as a selenoprotein antioxidant enzyme, is widely found in the embryo, testis, brain, liver, heart, and photoreceptor cells. Moreover, it is shown that GPX4 elicits diverse biological functions by suppressing phospholipid hydroperoxide at the expense of decreased glutathione (GSH), including loss of neurons, autophagy, cell repair, inflammation, ferroptosis, apoptosis, and oxidative stress. Interestingly, these processes are intimately related to the occurrence of fibrotic disease. Recently, GPX4 has been reported to exhibit a decline in fibrotic disease and inhibit fibrosis, suggesting that alterations of GPX4 can change the course or dictate the outcome of fibrotic disease. In this review, we summarize the role and underlying mechanisms of GPX4 in fibrosis diseases such as lung fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, and myelofibrosis.
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Affiliation(s)
- Zhaobing Li
- Department of Cardiology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunnan, China
| | - Zigui Zhu
- Department of Intensive Care Units, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, Hengyang, Hunnan, China
| | - Yulu Liu
- Department of Intensive Care Units, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, Hengyang, Hunnan, China
| | - Yannan Liu
- School of Nursing, Hunan University of Medicine, Huaihua, Hunan, China
| | - Hong Zhao
- School of Nursing, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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15
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Guo X, Zhang J, Han X, Wang G. LncRNA SNHG1 Delayed Fracture Healing via Modulating miR-181a-5p/PTEN Axis. J INVEST SURG 2022; 35:1304-1312. [PMID: 35263556 DOI: 10.1080/08941939.2022.2048926] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Xiuquan Guo
- Department of Spinal Surgery, Zhucheng People’s Hospital, Weifang, Shandong, China
| | - Jialiang Zhang
- Zhucheng Linjia Village Central Health Center, Weifang, Shandong, China
| | - Xuemei Han
- Zhucheng Longdu Health Center, Weifang, Shandong, China
| | - Ganggang Wang
- Department of Hand and Foot Surgery, Zhucheng People’s Hospital, Weifang, Shandong, China
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Zhu J, Guo Y. Circ_0020093 Overexpression Alleviates Interleukin-1 Beta-induced Inflammation, Apoptosis and Extracellular Matrix Degradation in Human Chondrocytes by Targeting the miR-181a-5p/ERG Pathway. Immunol Invest 2022; 51:1660-1677. [PMID: 35012421 DOI: 10.1080/08820139.2021.2021938] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Osteoarthritis (OA) is a well-known chronic degenerative joint disease, with multiple changes in the phenotype of chondrocytes. Circular RNAs (circRNAs) have been shown to be involved in various human diseases, including OA. The purpose of this study was to determine the role of circ_0020093 in OA pathological changes in vitro. C28/I2 cells were treated with interleukin-1 beta (IL-1β) to mimic OA pathological conditions. The expression levels of circ_0020093, miR-181a-5p and ETS-related gene (ERG) mRNA were measured by quantitative real-time PCR (qRT-PCR). For functional analyses, cell proliferative capacity was detected using EdU assay and CCK-8 assay. Inflammatory response was assessed by determining the release of pro-inflammatory factors using ELISA kits. Cell apoptosis was examined by flow cytometry assay. The levels of apoptosis-related proteins and extracellular matrix (ECM)-associated proteins were assessed by Western blot. The binding relationship between miR-181a-5p and circ_0020093 or ERG was confirmed by RNA pull-down assay, dual-luciferase reporter assay or RIP assay. The expression level of circ_0020093 was decreased in IL-1β-treated C28/I2 cells. Circ_0020093 overexpression relieved inflammatory responses, cell apoptosis and ECM degradation in IL-1β-induced C28/I2 cells. Circ_0020093 directly targeted miR-181a-5p, and miR-181a-5p bound to the 3' -untranslated region (3'UTR) of ERG to regulate ERG expression. Circ_0020093 overexpression promoted the expression of ERG by sponging miR-181a-5p. Rescue experiments showed that miR-181a-5p overexpression or ERG knockdown could reverse the inhibitory effects of circ_0020093 overexpression on the pathological changes in IL-1β-induced C28/I2 cells. Circ_0020093 overexpression alleviated IL-1β-induced human chondrocyte inflammatory injury, apoptosis and ECM degradation by targeting miR-181a-5p/ERG pathway.
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Affiliation(s)
- Jun Zhu
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang City, Hubei Province, China
| | - Yongchun Guo
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang City, Hubei Province, China
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Abstract
Aims Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results MDD has a significant genetic correlation with OA (rg = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (bxy = 0.24) and genetic liability to OA conferred a causal effect on MDD (bxy = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22.
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Affiliation(s)
- Fuquan Zhang
- Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Shuquan Rao
- State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Ancha Baranova
- School of Systems Biology, George Mason University, Fairfax, Virginia, USA.,Research Centre for Medical Genetics, Moscow, Russia
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Wang N, Xie M, Lei G, Zeng C, Yang T, Yang Z, Wang Y, Li J, Wei J, Tian J, Yang T. A Cross-Sectional Study of Association between Plasma Selenium Levels and the Prevalence of Osteoarthritis: Data from the Xiangya Osteoarthritis Study. J Nutr Health Aging 2022; 26:197-202. [PMID: 35166315 DOI: 10.1007/s12603-022-1739-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Selenium plays an indispensable role in antioxidant and antiinflammation processes. Oxidative stress and inflammation have been hypothesized to be involved in the pathogenesis of cartilage degeneration. We sought to examine the association between plasma selenium levels and the prevalence of radiographic osteoarthritis (ROA). DESIGN A population-based cross-sectional study. SETTING AND PARTICIPANTS Individuals aged ≥ 50 years were retrieved from the Xiangya Osteoarthritis (XO) Study, a community-based study conducted among the residents of the rural areas of China. METHODS Plasma selenium concentration was measured by inductively coupled plasma-dynamic reaction cell-mass spectrometry. ROA was defined as Kellgren/Lawrence score ≥ 2 in at least one knee, hip or hand joint. The association between plasma selenium levels and ROA was evaluated by applying logistic and spline regression. RESULTS A total of 1,032 subjects (women: 52.5%; mean age: 63.1 years; ROA prevalence: 45.4%) were included. Compared with the highest tertile, the odds ratios (ORs) for ROA were 1.24 (95% confidence interval [CI]: 0.91 to 1.68) and 1.77 (95% CI: 1.31 to 2.40) in the middle and lowest tertile of plasma selenium, respectively (P for trend<0.05). The results were not changed materially with adjustment of potential confounders. In addition, subjects who had lower plasma selenium levels exhibited a higher prevalence of ROA in a dose-response relationship manner (P=0.005). CONCLUSION This study suggests that subjects with lower levels of plasma selenium exhibited a higher prevalence of ROA in a dose-response relationship manner. However, additional studies are still needed to verify the potential causal relationship.
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Affiliation(s)
- N Wang
- Tuo Yang, Health Management Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China, 410008, Tel: 18711019415, E-mail: ; Jian Tian, Department of Orthopaedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China, 410008, Tel: 15116331787, E-mail:
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Zhai Z, Mu T, Zhao L, Li Y, Zhu D, Pan Y. MiR-181a-5p facilitates proliferation, invasion, and glycolysis of breast cancer through NDRG2-mediated activation of PTEN/AKT pathway. Bioengineered 2021; 13:83-95. [PMID: 34951340 PMCID: PMC8805873 DOI: 10.1080/21655979.2021.2006974] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of breast cancer. In this research, we explored the involvement of miR-181a-5p in the progression of breast cancer and investigated potential molecular mechanisms. Firstly, the miR-181a-5p and N-myc downstream-regulated gene (NDRG) 2 expression was detected by real-time quantitative polymerase chain reaction. Cellular processes were assessed using Cell Counting Kit 8, Bromodeoxyuridine, colony formation and transwell assays. HK2, PKM2 and LDHA activities were assessed by ELISA. The combination between miR-181a-5p was assessed by dual-luciferase reporter assay and RNA pull-down assay. The results indicated that miR-181a-5p levels were upregulated and NDRG2 levels were downregulated in breast cancer, leading to poor prognosis. Silencing of miR-181a-5p inhibited cell proliferation, invasion, glycolysis, and xenograft tumor growth, while enhanced miR-181a-5p got the opposite results. Furthermore, NDRG2 acts as a target of miR-181a-5p. Knockout of NDRG2 facilitated biological behaviors and meanwhile enhanced phosphorylation (p)-PTEN and p-AKT levels. Rescue experiments showed that restoring NDRG2 abolished the effects caused by miR-181a-5p in breast cancer cells. In conclusion, miR-181a-5p facilitated tumor progression through NDRG2-induced activation of PTEN/AKT signaling pathway of breast cancer, suggesting that focusing on miR-181a-5p may provide new insight for breast cancer therapy. Abbreviations Brdu: Bromodeoxyuridine; CCK-8: Cell Counting Kit-8; miRNA: microRNAs; mut: mutant; RT-qPCR: real-time quantitative polymerase chain reaction; UTR: untranslated region; WT: wild-type
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Affiliation(s)
- Zhen Zhai
- Breast Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China
| | - Tianlong Mu
- Breast Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China
- Pathology Department, Dongfang Hostipal Beijing University of Chinese Medicine, Beijing, China
| | - Lina Zhao
- Breast Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China
| | - Yiliang Li
- Breast Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China
| | - Dongsheng Zhu
- Breast Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China
| | - Yanshu Pan
- Periodical Center, Beijing University of Chinese Medicine, Beijing, China
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Letizia Mauro G, Scaturro D, Gimigliano F, Paoletta M, Liguori S, Toro G, Iolascon G, Moretti A. Physical Agent Modalities in Early Osteoarthritis: A Scoping Review. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:1165. [PMID: 34833383 PMCID: PMC8619194 DOI: 10.3390/medicina57111165] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 10/22/2021] [Accepted: 10/25/2021] [Indexed: 02/05/2023]
Abstract
Early osteoarthritis (EOA) still represents a challenge for clinicians. Although there is no consensus on its definition and diagnosis, a prompt therapeutic intervention in the early stages can have a significant impact on function and quality of life. Exercise remains a core treatment for EOA; however, several physical modalities are commonly used in this population. The purpose of this paper is to investigate the role of physical agents in the treatment of EOA. A technical expert panel (TEP) of 8 medical specialists with expertise in physical agent modalities and musculoskeletal conditions performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP searched for evidence of the following physical modalities in the management of EOA: "Electric Stimulation Therapy", "Pulsed Electromagnetic field", "Low-Level Light Therapy", "Laser Therapy", "Magnetic Field Therapy", "Extracorporeal Shockwave Therapy", "Hyperthermia, Induced", "Cryotherapy", "Vibration therapy", "Whole Body Vibration", "Physical Therapy Modalities". We found preclinical and clinical data on transcutaneous electrical nerve stimulation (TENS), extracorporeal shockwave therapy (ESWT), low-intensity pulsed ultrasound (LIPUS), pulsed electromagnetic fields stimulation (PEMF), and whole-body vibration (WBV) for the treatment of knee EOA. We found two clinical studies about TENS and PEMF and six preclinical studies-three about ESWT, one about WBV, one about PEMF, and one about LIPUS. The preclinical studies demonstrated several biological effects on EOA of physical modalities, suggesting potential disease-modifying effects. However, this role should be better investigated in further clinical studies, considering the limited data on the use of these interventions for EOA patients.
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Affiliation(s)
- Giulia Letizia Mauro
- Department of Surgery, Oncology, and Stomatology, University of Palermo, 90133 Palermo, Italy; (G.L.M.); (D.S.)
| | - Dalila Scaturro
- Department of Surgery, Oncology, and Stomatology, University of Palermo, 90133 Palermo, Italy; (G.L.M.); (D.S.)
| | - Francesca Gimigliano
- Department of Physical and Mental Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy;
| | - Marco Paoletta
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (S.L.); (G.T.); (G.I.); (A.M.)
| | - Sara Liguori
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (S.L.); (G.T.); (G.I.); (A.M.)
| | - Giuseppe Toro
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (S.L.); (G.T.); (G.I.); (A.M.)
| | - Giovanni Iolascon
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (S.L.); (G.T.); (G.I.); (A.M.)
| | - Antimo Moretti
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (S.L.); (G.T.); (G.I.); (A.M.)
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Yue Y, Zhibo S, Feng L, Yuanzhang B, Fei W. SNHG5 protects chondrocytes in interleukin-1β-stimulated osteoarthritis via regulating miR-181a-5p/TGFBR3 axis. J Biochem Mol Toxicol 2021; 35:e22866. [PMID: 34369033 DOI: 10.1002/jbt.22866] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 02/22/2021] [Accepted: 07/20/2021] [Indexed: 12/19/2022]
Abstract
Long noncoding RNAs (lncRNAs) have been considered as important modulators in the development of osteoarthritis. The present study investigates whether there is a link between lncRNA small nucleolar RNA host gene 5 (SNHG5) and osteoarthritis pathogenesis, and the underlying molecular mechanism. To establish an in vitro model of osteoarthritis, interleukin 1β (IL-1β) was used to treat chondrocytes (C20/A4 cells) for mimicking the inflammatory condition in osteoarthritis pathogenesis. SNHG5 and miR-181a-5p expression levels were then detected in cartilage tissues of osteoarthritis patients and C20/A4 cells by quantitative polymerase chain reaction (qPCR). Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were applied for detecting the viability of chondrocytes, and the apoptosis of chondrocytes was examined through caspase-3 activity assay and flow cytometry analysis. Western blot and qPCR were employed for determining the expression levels of TGFBR3, ADAMTS5, and MMP-13. The regulatory relationships among SNHG5, miR-181a-5p, and TGFBR3 were verified by RNA immunoprecipitation and dual-luciferase reporter assays. The expression levels of SNHG5 and TGFBR3 were markedly decreased, and miR-181a-5p expression was enhanced in osteoarthritis tissues and chondrocytes treated with IL-1β. SNHG5 knockdown inhibited the viability of chondrocytes, induced apoptosis, and promoted the expression levels of ADAMTS5 and MMP-13. Conversely, SNHG5 overexpression could counteract the effects of IL-1β, increase the viability of chondrocytes and suppress apoptosis. Mechanically, SNHG5 positively regulated TGFBR3 expression via sponging miR-181a-5p. Moreover, miR-181a-5p overexpression and TGFBR3 knockdown counteracted the effects of SNHG5 on chondrocytes. SNHG5 can probably protect chondrocytes from the inflammatory response and reduce the degradation of the extracellular matrix via modulating the miR-181a-5p/TGFBR3 axis.
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Affiliation(s)
- Yang Yue
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Sun Zhibo
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Liu Feng
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Bai Yuanzhang
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Wu Fei
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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22
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Huang Z, Ma W, Xiao J, Dai X, Ling W. CircRNA_0092516 regulates chondrocyte proliferation and apoptosis in osteoarthritis through the miR-337-3p/PTEN axis. J Biochem 2021; 169:467-475. [PMID: 33135071 DOI: 10.1093/jb/mvaa119] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 10/19/2020] [Indexed: 11/13/2022] Open
Abstract
The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases. Here, we probed into the potential mechanism of circRNA_0092516 in osteoarthritis (OA). The expression of circRNA_0092516 was tested by quantitative real-time PCR. MTT, flow cytometry and western blot were applied to confirm the functions of circRNA_0092516 in vitro. Besides, RNA pull-down and dual-luciferase reporter gene experiments were applied to probe into the mechanism. circRNA_0092516 was raised in the tissues of OA patients and chondrocytes stimulated by IL-1β. The potential mechanism analysis expounded that circRNA_0092516 bound to miR-337-3p, and the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/phosphatase and tensin homolog (PTEN) axis, thereby improving OA. In-vivo experiments expounded that circRNA_0092516 regulated cartilage production through miR-337-3p. Overall, our data expounded that the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/PTEN axis, eventually slowed down the progress of OA.
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Affiliation(s)
- Zhihui Huang
- Department of Orthopedics, The Third Affiliated Hospital of Suchow University, No. 185 Juqian Road, Changzhou 213000, Jiangsu Province, China
| | - Wenming Ma
- Department of Orthopedics, The Third Affiliated Hospital of Suchow University, No. 185 Juqian Road, Changzhou 213000, Jiangsu Province, China
| | - Jinhuai Xiao
- Department of Orthopedics, The Third Affiliated Hospital of Suchow University, No. 185 Juqian Road, Changzhou 213000, Jiangsu Province, China
| | - Xiaoyu Dai
- Department of Orthopedics, The Third Affiliated Hospital of Suchow University, No. 185 Juqian Road, Changzhou 213000, Jiangsu Province, China
| | - Weiqi Ling
- Department of Orthopedics, The Third Affiliated Hospital of Suchow University, No. 185 Juqian Road, Changzhou 213000, Jiangsu Province, China
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23
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Fu R, Wang Y, Wang Y. Silencing microRNA-181a-5p suppresses malignant behavior of lacrimal adenoid cystic carcinoma cells by upregulating large tumor suppressor 2. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2020; 13:2419-2426. [PMID: 33042355 PMCID: PMC7539885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 06/29/2020] [Indexed: 06/11/2023]
Abstract
To uncover the effect of miR-181a-5p regulating large tumor suppressor 2 (LATS2) in biologic processes of adenoid cystic carcinoma (ACC) cells, miR-181a-5p and LATS2 expression in lacrimal ACC (LACC) tissues were assessed. The ACC cell lines were respectively treated with altered miR-181a-5p or LATS2 to determine the biologic functions in ACC cells. Binding ability of miR-181a-5p and LATS2 was confirmed. Tumor growth in vivo was assessed as well. MiR-181a-5p was upregulated while LATS2 was downregulated in LACC tissues. Reduced miR-181a-5p restrained malignant phenotype of ACC cells and decelerated xenograft growth. Conversely, LATS2 reduction had opposite effects compared to miR-181a-5p knockdown on ACC cells. Furthermore, downregulated LATS2 could abolish the alterations in ACC cells induced by miR-181a-5p silencing. MiR-181a-5p inhibition upregulated LATS2 to suppress malignant behavior of ACC cells in vivo and in vitro.
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Affiliation(s)
- Rongrong Fu
- Department of Orbital Plastic Surgery, The 4th People's Hospital of Shenyang Shenyang 110000, Liaoning, P. R. China
| | - Yingshuang Wang
- Department of Orbital Plastic Surgery, The 4th People's Hospital of Shenyang Shenyang 110000, Liaoning, P. R. China
| | - Yawen Wang
- Department of Orbital Plastic Surgery, The 4th People's Hospital of Shenyang Shenyang 110000, Liaoning, P. R. China
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24
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Kang D, Lee J, Wu C, Guo X, Lee BJ, Chun JS, Kim JH. The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies. Exp Mol Med 2020; 52:1198-1208. [PMID: 32788658 PMCID: PMC7423502 DOI: 10.1038/s12276-020-0408-y] [Citation(s) in RCA: 103] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 02/08/2020] [Accepted: 02/10/2020] [Indexed: 01/16/2023] Open
Abstract
As an essential nutrient and trace element, selenium is required for living organisms and its beneficial roles in human health have been well recognized. The role of selenium is mainly played through selenoproteins synthesized by the selenium metabolic system. Selenoproteins have a wide range of cellular functions including regulation of selenium transport, thyroid hormones, immunity, and redox homeostasis. Selenium deficiency contributes to various diseases, such as cardiovascular disease, cancer, liver disease, and arthropathy—Kashin–Beck disease (KBD) and osteoarthritis (OA). A skeletal developmental disorder, KBD has been reported in low-selenium areas of China, North Korea, and the Siberian region of Russia, and can be alleviated by selenium supplementation. OA, the most common form of arthritis, is a degenerative disease caused by an imbalance in matrix metabolism and is characterized by cartilage destruction. Oxidative stress serves as a major cause of the initiation of OA pathogenesis. Selenium deficiency and dysregulation of selenoproteins are associated with impairments to redox homeostasis in cartilage. We review the recently explored roles of selenium metabolism and selenoproteins in cartilage with an emphasis on two arthropathies, KBD and OA. Moreover, we discuss the potential of therapeutic strategies targeting the biological functions of selenium and selenoproteins for OA treatment. Selenium, a micronutrient found in brazil nuts, shiitake mushrooms, and most meats, may aid in treating joint diseases, including the most common form of arthritis, osteoarthritis (OA). In addition to thyroid hormone metabolism and immunity, selenium is important in antioxidant defense. Oxidative damage can destroy cartilage and harm joints, and selenium deficiency is implicated in several joint diseases. Jin-Hong Kim at Seoul National University in South Korea and co-workers reviewed selenium metabolism, focusing on OA and and Kashin–Beck disease, a skeletal development disorder prevalent in selenium-deficient areas of northeast Asia. They report that selenium-containing proteins protect cells against oxidative damage and that selenium is crucial to cartilage production. Further investigation of selenium metabolism may point the way to new treatments for OA and other joint diseases.
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Affiliation(s)
- Donghyun Kang
- Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea.,Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea
| | - Jeeyeon Lee
- Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea.,Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea
| | - Cuiyan Wu
- School of Public Health, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xiong Guo
- School of Public Health, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Byeong Jae Lee
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.,Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, South Korea
| | - Jang-Soo Chun
- National Creative Research Initiatives Center for Osteoarthritis Pathogenesis and School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, South Korea
| | - Jin-Hong Kim
- Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea. .,Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea. .,Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, South Korea.
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25
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Zhang X, Wang L, Li H, Zhang L, Zheng X, Cheng W. Crosstalk between noncoding RNAs and ferroptosis: new dawn for overcoming cancer progression. Cell Death Dis 2020; 11:580. [PMID: 32709863 PMCID: PMC7381619 DOI: 10.1038/s41419-020-02772-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 07/06/2020] [Accepted: 07/10/2020] [Indexed: 02/06/2023]
Abstract
Cancer progression including proliferation, metastasis, and chemoresistance has become a serious hindrance to cancer therapy. This phenomenon mainly derives from the innate insensitive or acquired resistance of cancer cells to apoptosis. Ferroptosis is a newly discovered mechanism of programmed cell death characterized by peroxidation of the lipid membrane induced by reactive oxygen species. Ferroptosis has been confirmed to eliminate cancer cells in an apoptosis-independent manner, however, the specific regulatory mechanism of ferroptosis is still unknown. The use of ferroptosis for overcoming cancer progression is limited. Noncoding RNAs have been found to play an important roles in cancer. They regulate gene expression to affect biological processes of cancer cells such as proliferation, cell cycle, and cell death. Thus far, the functions of ncRNAs in ferroptosis of cancer cells have been examined, and the specific mechanisms by which noncoding RNAs regulate ferroptosis have been partially discovered. However, there is no summary of ferroptosis associated noncoding RNAs and their functions in different cancer types. In this review, we discuss the roles of ferroptosis-associated noncoding RNAs in detail. Moreover, future work regarding the interaction between noncoding RNAs and ferroptosis is proposed, the possible obstacles are predicted and associated solutions are put forward. This review will deepen our understanding of the relationship between noncoding RNAs and ferroptosis, and provide new insights in targeting noncoding RNAs in ferroptosis associated therapeutic strategies.
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Affiliation(s)
- Xuefei Zhang
- Department of Ultrasonography, Harbin Medical University Cancer Hospital, 150 Haping Road, 150040, Harbin, China
| | - Lingling Wang
- Department of Ultrasonography, Harbin Medical University Cancer Hospital, 150 Haping Road, 150040, Harbin, China
| | - Haixia Li
- Department of Ultrasonography, Harbin Medical University Cancer Hospital, 150 Haping Road, 150040, Harbin, China
| | - Lei Zhang
- Department of Ultrasonography, Harbin Medical University Cancer Hospital, 150 Haping Road, 150040, Harbin, China.
| | - Xiulan Zheng
- Department of Ultrasonography, Harbin Medical University Cancer Hospital, 150 Haping Road, 150040, Harbin, China.
| | - Wen Cheng
- Department of Ultrasonography, Harbin Medical University Cancer Hospital, 150 Haping Road, 150040, Harbin, China.
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26
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Stanishevska NV. Selenoproteins and their emerging roles in signaling pathways. REGULATORY MECHANISMS IN BIOSYSTEMS 2020. [DOI: 10.15421/022028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
The functional activity of selenoproteins has a wide range of effects on complex pathogenetic processes, including teratogenesis, immuno-inflammatory, neurodegenerative. Being active participants and promoters of many signaling pathways, selenoproteins support the lively interest of a wide scientific community. This review is devoted to the analysis of recent data describing the participation of selenoproteins in various molecular interactions mediating important signaling pathways. Data processing was carried out by the method of complex analysis. For convenience, all selenoproteins were divided into groups depending on their location and function. Among the group of selenoproteins of the ER membrane, selenoprotein N affects the absorption of Ca2+ by the endoplasmic reticulum mediated by oxidoreductin (ERO1), a key player in the CHOP/ERO1 branch, a pathogenic mechanism that causes myopathy. Another selenoprotein of the ER membrane selenoprotein K binding to the DHHC6 protein affects the IP3R receptor that regulates Ca2+ flux. Selenoprotein K is able to affect another protein of the endoplasmic reticulum CHERP, also appearing in Ca2+ transport. Selenoprotein S, associated with the lumen of ER, is able to influence the VCP protein, which ensures the incorporation of selenoprotein K into the ER membrane. Selenoprotein M, as an ER lumen protein, affects the phosphorylation of STAT3 by leptin, which confirms that Sel M is a positive regulator of leptin signaling. Selenoprotein S also related to luminal selenoproteins ER is a modulator of the IRE1α-sXBP1 signaling pathway. Nuclear selenoprotein H will directly affect the suppressor of malignant tumours, p53 protein, the activation of which increases with Sel H deficiency. The same selenoprotein is involved in redox regulation. Among the cytoplasmic selenoproteins, abundant investigations are devoted to SelP, which affects the PI3K/Akt/Erk signaling pathway during ischemia/reperfusion, is transported into the myoblasts through the plasmalemma after binding to the apoER2 receptor, and into the neurons to the megaline receptor and in general, selenoprotein P plays the role of a pool that stores the necessary trace element and releases it, if necessary, for vital selenoproteins. The thioredoxin reductase family plays a key role in the invasion and metastasis of salivary adenoid cystic carcinoma through the influence on the TGF-β-Akt/GSK-3β pathway during epithelial-mesenchymal transition. The deletion of thioredoxin reductase 1 affects the levels of messengers of the Wnt/β-catenin signaling pathway. No less studied is the glutathione peroxidase group, of which GPX3 is able to inhibit signaling in the Wnt/β-catenin pathway and thereby inhibit thyroid metastasis, as well as suppress protein levels in the PI3K/Akt/c-fos pathway. A key observation is that in cases of carcinogenesis, a decrease in GPX3 and its hypermethylation are almost always found. Among deiodinases, deiodinase 3 acts as a promoter of the oncogenes BRAF, MEK or p38, while stimulating a decrease in the expression of cyclin D1. The dependence of the level of deiodinase 3 on the Hedgehog (SHH) signaling pathway is also noted. Methionine sulfoxide reductase A can compete for the uptake of ubiquitin, reduce p38, JNK and ERK promoters of the MAPK signaling pathway; methionine sulfoxide reductase B1 suppresses MAPK signaling messengers, and also increases PARP and caspase 3.
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27
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Yan X, Chen YR, Song YF, Yang M, Ye J, Zhou G, Yu JK. Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering. Front Pharmacol 2020; 10:1534. [PMID: 31992984 PMCID: PMC6970981 DOI: 10.3389/fphar.2019.01534] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 11/27/2019] [Indexed: 12/20/2022] Open
Abstract
Significant progress in osteochondral tissue engineering has been made for biomaterials designed to deliver growth factors that promote tissue regeneration. However, due to diffusion characteristics of hydrogels, the accurate delivery of signaling molecules remains a challenge. In comparison to the direct delivery of growth factors, gene therapy can overcome these challenges by allowing the simultaneous delivery of growth factors and transcription factors, thereby enhancing the multifactorial processes of tissue formation. Scaffold-based gene therapy provides a promising approach for tissue engineering through transfecting cells to enhance the sustained expression of the protein of interest or through silencing target genes associated with bone and joint disease. Reports of the efficacy of gene therapy to regenerate bone/cartilage tissue regeneration are widespread, but reviews on osteochondral tissue engineering using scaffold-based gene therapy are sparse. Herein, we review the recent advances in gene therapy with a focus on tissue engineering scaffolds for osteochondral regeneration.
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Affiliation(s)
- Xin Yan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - You-Rong Chen
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Yi-Fan Song
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Meng Yang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Jing Ye
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Gang Zhou
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Jia-Kuo Yu
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
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28
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Jiang S, Liu Y, Xu B, Zhang Y, Yang M. Noncoding RNAs: New regulatory code in chondrocyte apoptosis and autophagy. WILEY INTERDISCIPLINARY REVIEWS-RNA 2020; 11:e1584. [PMID: 31925936 DOI: 10.1002/wrna.1584] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 11/13/2019] [Accepted: 12/20/2019] [Indexed: 12/11/2022]
Abstract
Osteoarthritis (OA) is a bone and joint disease characterized by progressive cartilage degradation. In the face of global trends of population aging, OA is expected to become the fourth most common disabling disease by 2020. Nevertheless, the detailed pathogenesis of OA has not yet been elucidated. Noncoding RNAs (ncRNAs), including long noncoding RNAs, microRNAs, and circular RNAs, do not encode proteins but have recently emerged as important regulators of apoptosis and autophagy of chondrocytes, thereby highlighting a potential role in chondrocyte injury leading to OA onset and progression. We here review recent findings on these regulatory roles of ncRNAs to provide new directions for research on the pathogenesis of OA and offer new therapeutic targets for prevention and treatment. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.
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Affiliation(s)
- Siyu Jiang
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Medical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang, China.,Department of Pharmacology, Guangdong Medical University, Zhanjiang, China
| | - Yi Liu
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Medical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang, China.,Department of Pharmacology, Guangdong Medical University, Zhanjiang, China
| | - Bilian Xu
- Department of Pharmacology, Guangdong Medical University, Zhanjiang, China
| | - Yan Zhang
- Operating Room, Tianjin Binhai New Area Tanggu Obstetrics and Gynecology Hospital, Tianjin, China
| | - Min Yang
- Shenzhen Ritzcon Biological Technology Co., LTD, Shenzhen, China
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29
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Yan L, Bai M, Xu J, Li X, Wu C, Zhou Y, Yan J, Zhang Z. Retracted Article: CircRNA PVT1 modulates cell metastasis via the miR-181a-5p/NEK7 axis and cisplatin chemoresistance through miR-181a-5p-mediated autophagy in non-small cell lung cancer. RSC Adv 2019; 9:42324-42334. [PMID: 35542851 PMCID: PMC9076563 DOI: 10.1039/c9ra08872e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 12/08/2019] [Indexed: 01/07/2023] Open
Abstract
In the initiation and evolution of human cancers, circular RNAs (circRNAs) act as crucial regulators. The aim of this report was to ascertain the functional mechanisms of circRNA plasmacytoma variant translocation 1 (circPVT1) in the metastasis and chemoresistance of non-small cell lung cancer (NSCLC). The levels of circPVT1, microRNA-181a-5p (miR-181a-5p) and non-inherited maternal antigens-related kinase 7 (NEK7) were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The levels of the associated proteins were determined through western blot. Cell counting kit-8 (CCK-8) and flow cytometry were used to assess the half inhibitory concentration (IC50) of cisplatin and cell apoptosis, respectively. Cell invasion was detected by transwell assay. A dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to confirm the target relation. The impact of circPVT1 on cisplatin chemoresistance in vivo was investigated using xenograft experiments. CircPVT1 and NEK7 were up-regulated and miR-181a-5p was down-regulated in NSCLC. CircPVT1 knockdown refrained the cisplatin chemoresistance and metastasis of NSCLC cells. MiR-181a-5p was a target of circPVT1 and circPVT1 inhibition alleviated the effects of a miR-181a-5p inhibitor on NSCLC cells. The decrease of circPVT1 accentuated the si-NEK7-inhibited metastasis by the miR-181a-5p/NEK7 axis and relieved the 3-methyladenine (3-MA)-promoted cisplatin chemoresistance by miR-181a-5p-mediated autophagy. Down-regulation of circPVT1 facilitated the cisplatin sensitivity of NSCLC cells in vivo. Due to the modulation of cell metastasis via the miR-181a-5p/NEK7 axis and cisplatin chemoresistance by miR-181a-5p-mediated autophagy in NSCLC, circPVT1 might act as an appreciable therapeutic marker for NSCLC. In the initiation and evolution of human cancers, circular RNAs (circRNAs) act as crucial regulators.![]()
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Affiliation(s)
- Limin Yan
- Department of Pathology
- Tangshan Gongren Hospital
- Tangshan 063000
- China
| | - Minghe Bai
- Department of Pathology
- Tangshan Gongren Hospital
- Tangshan 063000
- China
| | - Jinheng Xu
- Department of Pathology
- Tangshan Gongren Hospital
- Tangshan 063000
- China
| | - Xuemei Li
- Department of Pathology
- Tangshan Gongren Hospital
- Tangshan 063000
- China
| | - Chenpeng Wu
- Department of Pathology
- Tangshan Gongren Hospital
- Tangshan 063000
- China
| | - Yuntao Zhou
- Department of Center Labotarary
- Tangshan Gongren Hospital
- Tangshan 063000
- China
| | - Jidong Yan
- Department of Thoracic Surgery
- Tangshan Gongren Hospital
- Tangshan 063000
- China
| | - Zhiyong Zhang
- Department of Pathology
- Tangshan Gongren Hospital
- Tangshan 063000
- China
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