The regulatory activities of MALAT1 in the development of bone and cartilage diseases

Zhang, Di; Xue, Junmin; Peng, Fang Zheng

doi:10.3389/fendo.2022.1054827

Cited by 8 publications

(5 citation statements)

References 104 publications

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“…Therefore, cell‐specific targeting of Mgp in either chondrocytes or osteocytes may provide important data with regard to the role of Mgp in the maintenance of bone ECM and bone formation. Moreover, this co‐expression approach may be valuable in identifying noncoding RNAs that contribute to the regulation of BMD, as we found Malat1— a long noncoding RNA (lncRNA) that regulates osteogenesis ( 37,79–81,115 ) —as highly co‐expressed with VNN genes.…”

Section: Discussionmentioning

confidence: 99%

Single‐Cell Integration of BMD GWAS Results Prioritize Candidate Genes Influencing Age‐Related Bone Loss

2023

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The regulation of bone mineral density (BMD) is highly influenced by genetics and age. Although genome‐wide association studies (GWAS) for BMD have uncovered many genes through their proximity to associated variants (variant nearest‐neighbor [VNN] genes), the cell‐specific mechanisms of each VNN gene remain unclear. This is primarily due to the inability to prioritize these genes by cell type and age‐related expression. Using age‐related transcriptomics, we found that the expression of many VNN genes was upregulated in the bone and marrow from aged mice. Candidate genes from GWAS were investigated using single‐cell RNA‐sequencing (scRNA‐seq) datasets to enrich for cell‐specific expression signatures. VNN candidate genes are highly enriched in osteo‐lineage cells, osteocytes, hypertrophic chondrocytes, and Lepr+ mesenchymal stem cells. These data were used to generate a “blueprint” for Cre‐loxp mouse line selection for functional validation of candidate genes and further investigation of their role in BMD maintenance throughout aging. In VNN‐gene‐enriched cells, Sparc, encoding the extracellular matrix (ECM) protein osteonectin, was robustly expressed. This, along with expression of numerous other ECM genes, indicates that many VNN genes likely have roles in ECM deposition by osteoblasts. Overall, we provide data supporting streamlined translation of GWAS candidate genes to potential novel therapeutic targets for the treatment of osteoporosis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Single‐Cell Integration of BMD GWAS Results Prioritize Candidate Genes Influencing Age‐Related Bone Loss

2023

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“…It was observed that the hepatocyte growth factor increased MALAT1 expression and that the p53 TF was involved in the negative regulation of MALAT1 during liver regeneration. In other studies, MALAT1 expression was stimulated in the kidneys of diabetic mice by a high increase in glucose, which is positively related to serum creatinine and urinary albumin levels [49,50]. Returning to post-transcriptional regulation, Leucci et al [51] used the L428 and U87MG cell lines to prove that miR-9 regulates MALAT1 expression mediated by AGO2.…”

Section: Upstream Regulation Of Malat1 Gene Expressionmentioning

confidence: 99%

MALAT1: A Long Non-Coding RNA with Multiple Functions and Its Role in Processes Associated with Fat Deposition

Piórkowska,

Zygmunt,

Hunter

et al. 2024

Genes

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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) belongs to the lncRNA molecules, which are involved in transcriptional and epigenetic regulation and the control of gene expression, including the mechanism of chromatin remodeling. MALAT1 was first discovered during carcinogenesis in lung adenocarcinoma, hence its name. In humans, 66 of its isoforms have been identified, and in pigs, only 2 are predicted, for which information is available in Ensembl databases (Ensembl Release 111). MALAT1 is expressed in numerous tissues, including adipose, adrenal gland, heart, kidney, liver, ovary, pancreas, sigmoid colon, small intestine, spleen, and testis. MALAT1, as an lncRNA, shows a wide range of functions. It is involved in the regulation of the cell cycle, where it has pro-proliferative effects and high cellular levels during the G1/S and mitotic (M) phases. Moreover, it is involved in invasion, metastasis, and angiogenesis, and it has a crucial function in alternative splicing during carcinogenesis. In addition, MALAT1 plays a significant role in the processes of fat deposition and adipogenesis. The human adipose tissue stem cells, during differentiation into adipocytes, secrete MALAT1 as one the most abundant lncRNAs in the exosomes. MALAT1 expression in fat tissue is positively correlated with adipogenic FABP4 and LPL. This lncRNA is involved in the regulation of PPARγ at the transcription stage, fatty acid metabolism, and insulin signaling. The wide range of MALAT1 functions makes it an interesting target in studies searching for drugs to prevent obesity development in humans. In turn, in farm animals, it can be a source of selection markers to control the fat tissue content.

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“…The lncRNAs are a class of non-coding RNAs, which are longer than 200 nucleotides in length and play crucial roles in various cellular processes. Metastasis-associated lung adenocarcinoma transcript-1(MALAT1) is a highly conserved lncRNA that is closely asso-ciated with the initiation and development of bone and cartilage diseases [107]. Diabetes mellitus (DM) is a pathogenic condition associated with IDD.…”

Section: Regulation Of P38 Mapk By Non-coding Rnas In Iddmentioning

confidence: 99%

Stress-Activated Protein Kinases in Intervertebral Disc Degeneration: Unraveling the Impact of JNK and p38 MAPK

Li,

Zhang,

Yang

et al. 2024

Biomolecules

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Intervertebral disc degeneration (IDD) is a major cause of lower back pain. The pathophysiological development of IDD is closely related to the stimulation of various stressors, including proinflammatory cytokines, abnormal mechanical stress, oxidative stress, metabolic abnormalities, and DNA damage, among others. These factors prevent normal intervertebral disc (IVD) development, reduce the number of IVD cells, and induce senescence and apoptosis. Stress-activated protein kinases (SAPKs), particularly, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), control cell signaling in response to cellular stress. Previous studies have shown that these proteins are highly expressed in degenerated IVD tissues and are involved in complex biological signal-regulated processes. Therefore, we summarize the research reports on IDD related to JNK and p38 MAPK. Their structure, function, and signal regulation mechanisms are comprehensively and systematically described and potential therapeutic targets are proposed. This work could provide a reference for future research and help improve molecular therapeutic strategies for IDD.

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The regulatory activities of MALAT1 in the development of bone and cartilage diseases

Cited by 8 publications

References 104 publications

Single‐Cell Integration of BMD GWAS Results Prioritize Candidate Genes Influencing Age‐Related Bone Loss

Single‐Cell Integration of BMD GWAS Results Prioritize Candidate Genes Influencing Age‐Related Bone Loss

MALAT1: A Long Non-Coding RNA with Multiple Functions and Its Role in Processes Associated with Fat Deposition

Stress-Activated Protein Kinases in Intervertebral Disc Degeneration: Unraveling the Impact of JNK and p38 MAPK

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