ArticleJournal of orthopaedic surgery and research2024
CYLD alleviates NLRP3 inflammasome-mediated pyroptosis in osteoporosis by deubiquitinating WNK1.
Article in Journal of orthopaedic surgery and research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- From mechanisms to therapeutics: a narrative review on pyroptosis and autophagy in osteoporosis.Annals of medicine · 2025Pooled it
- Hydroxytyrosol attenuates obesity-induced myocardial fibrosis by inhibiting NLRP3/CYLD/NOX4 mediated oxidative stress.NPJ science of food · 2026Article
- Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes.Cellular and molecular life sciences : CMLS · 2026Article
- Ubiquitin-proteasome system regulation of bone remodeling in postmenopausal osteoporosis.Frontiers in cell and developmental biology · 2026Review
- Mechanism of CGF in osteogenic differentiation of periodontal ligament stem cells through the Wnt pathway.Organogenesis · 2025Article
- WNK1 Alleviates Chloride Efflux-Induced NLRP3 Inflammasome Activation and Subsequent Neuroinflammation in Early Brain Injury Following Subarachnoid Hemorrhage.Neuroscience bulletin · 2025Article
- NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting.Journal of cellular and molecular medicine · 2025Review
- NRBP1 pseudokinase binds to and activates the WNK pathway in response to osmotic stress.Science advances · 2025Article
- Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone.Biomolecules · 2025Review
- Exploring Ubiquitination in Spinal Cord Injury Therapy: Multifaceted Targets and Promising Strategies.Neurochemical research · 2025Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteoporosis (OP) is the result of bone mass reduction and bone structure disorder. Bone marrow mesenchymal stem cells (BMSCs) are the main source of osteogenic precursor cells involved in adult bone remodeling. The involvement of the deubiquitinating enzyme CYLD in OP has recently been discovered. However, the detailed role and mechanism of CYLD remain unknown.
methodsThe OP mouse model was established by performing ovariectomy (OVX) on mice. Hematoxylin and eosin staining, Masson and Immunohistochemical staining were used to assess pathologic changes. Real-time quantitative PCR, Western blot, and immunofluorescence were employed to assess the expression levels of CYLD, WNK1, NLRP3 and osteogenesis-related molecules. The binding relationship between CYLD and WNK1 was validated through a co-immunoprecipitation assay. The osteogenic capacity of BMSCs was determined using Alkaline phosphatase (ALP) and alizarin red staining (ARS). Protein ubiquitination was evaluated by a ubiquitination assay.
resultsThe levels of both CYLD and WNK1 were decreased in bone tissues and BMSCs of OVX mice. Overexpression of CYLD or WNK1 induced osteogenic differentiation in BMSCs. Additionally, NLRP3 inflammation was activated in OVX mice, but its activation was attenuated upon overexpression of CYLD or WNK1. CYLD was observed to reduce the ubiquitination of WNK1, thereby enhancing its protein stability and leading to the inactivation of NLRP3 inflammation. However, the protective effects of CYLD on osteogenic differentiation and NLRP3 inflammation inactivation were diminished upon silencing of WNK1.
conclusionCYLD mitigates NLRP3 inflammasome-triggered pyroptosis in osteoporosis through its deubiquitination of WNK1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.