ArticleCell death & disease2021
DUSP6 expression is associated with osteoporosis through the regulation of osteoclast differentiation via ERK2/Smad2 signaling.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Identification of potential diagnostic and therapeutic apoptosis-related casual targets for osteoporosis: an integrated multi-omics analysis.Journal of bone and mineral metabolism · 2026Pooled it
- KLF6 regulates osteoclastogenesis through DUSP16 in OVX-induced bone loss.Science China. Life sciences · 2026Article
- Diosgenin activates ERα-dependent PI3K/AKT/GSK3β signaling to enhance brain-derived serotonin and alleviate postmenopausal bone loss.Journal of advanced research · 2026Article
- Case Report: dynamic monocyte reprogramming during ALSS therapy in type B HBV-ACLF revealed by single-cell transcriptomics.Frontiers in immunology · 2026Article
- Micropatterning and Nanodropletting of Titanium by Shifted Surface Laser Texturing Significantly Enhances In Vitro Osteogenesis of Healthy and Osteoporotic Mesenchymal Stromal Cells.Journal of functional biomaterials · 2025Article
- Genome-Wide Association Study of Body Size Traits in Luning Chickens Using Whole-Genome Sequencing.Animals : an open access journal from MDPI · 2025Article
- PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.Zoological research · 2024Article
- Farnesoid X receptor: From Structure to Function and Its Pharmacology in Liver Fibrosis.Aging and disease · 2024Review
- Overexpression of CENPU promotes cancer growth and metastasis and is associated with poor survival in patients with nasopharyngeal carcinoma.Translational cancer research · 2024Article
- Review
- Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning.NPJ biofilms and microbiomes · 2024Article
- Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets.Molecular medicine (Cambridge, Mass.) · 2024Review
- Noncoding RNAs: the crucial role of programmed cell death in osteoporosis.Frontiers in cell and developmental biology · 2024Review
- Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.Frontiers in pharmacology · 2024Review
- The miR-181 family: Wide-ranging pathophysiological effects on cell fate and function.Journal of cellular physiology · 2023Review
- Long noncoding RNA GK-IT1 promotes esophageal squamous cell carcinoma by regulating MAPK1 phosphorylation.Cancer medicine · 2022Article
- STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis.Cell communication and signaling : CCS · 2022Review
- Bisphosphonate-based hydrogel mediates biomimetic negative feedback regulation of osteoclastic activity to promote bone regeneration.Bioactive materials · 2022Article
- microRNA-211-5p predicts the progression of postmenopausal osteoporosis and attenuates osteogenesis by targeting dual specific phosphatase 6.Bioengineered · 2022Article
- Gut Metabolite Urolithin A Inhibits Osteoclastogenesis and Senile Osteoporosis by Enhancing the Autophagy Capacity of Bone Marrow Macrophages.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Osteoporosis-related fractures, such as femoral neck and vertebral fractures, are common in aged people, resulting in increased disability rate and health-care costs. Thus, it is of great importance to clarify the mechanism of osteoclast-related osteoporosis and find effective ways to avoid its complication. In this study, gene expression profile analysis and real-time polymerase chain reaction revealed that DUSP6 expression was suppressed in human and mice osteoporosis cases. In vitro experiments confirmed that DUSP6 overexpression prevented osteoclastogenesis, whereas inhibition of DUSP6 by small interference RNA or with a chemical inhibitor, (E/Z)-BCI, had the opposite effect. (E/Z)-BCl significantly accelerated the bone loss process in vivo by enhancing osteoclastogenesis. Bioinformatics analyses and in vitro experiments indicated that miR-181a was an upstream regulator of DUSP6. Moreover, miR-181a positively induced the differentiation and negatively regulated the apoptosis of osteoclasts via DUSP6. Furthermore, downstream signals by ERK2 and SMAD2 were also found to be involved in this process. Evaluation of ERK2-deficiency bone marrow-derived macrophages confirmed the role of ERK2 signaling in the DUSP6-mediated osteoclastogenesis. Additionally, immunoprecipitation assays confirmed that DUSP6 directly modified the phosphorylation status of SMAD2 and the subsequent nuclear transportation of NFATC1 to regulate osteoclast differentiation. Altogether, this study demonstrated for the first time the role of miRNA-181a/DUSP6 in the progression of osteoporosis via the ERK2 and SMAD2 signaling pathway. Hence, DUSP6 may represent a novel target for the treatment of osteoclast-related diseases in the future.
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