ArticleArthritis & rheumatology (Hoboken, N.J.)2019
Activation of the Peroxisome Proliferator-Activated Receptor γ Coactivator 1β/NFATc1 Pathway in Circulating Osteoclast Precursors Associated With Bone Destruction in Rheumatoid Arthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- In Silico Investigation RevealsMedical sciences (Basel, Switzerland) · 2026Article
- Early menopause is associated with higher disease activity independent of inflammation in postmenopausal-onset rheumatoid arthritis.BMC women's health · 2025Observational
- Erianin serves as an NFATc1 inhibitor to prevent breast cancer-induced osteoclastogenesis and bone destruction.Journal of advanced research · 2025Article
- MTHFD2 promotes osteoclastogenesis and bone loss in rheumatoid arthritis by enhancing CKMT1-mediated oxidative phosphorylation.BMC medicine · 2025Article
- Should we use bisphosphonates to treat bone complications in sickle cell disease?Hematology. American Society of Hematology. Education Program · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- A Review of Proposed Mechanisms in Rheumatoid Arthritis and Therapeutic Strategies for the Disease.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Review
- RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1β- and RNA-dependent co-activator of osteoclast gene expression.Molecular cell · 2023Article
- GelMA Hydrogel as a Promising Delivery System for Osthole in the Treatment of Rheumatoid Arthritis: Targeting the miR-1224-3p/AGO1 Axis.International journal of molecular sciences · 2023Article
- Gsmtx4 Alleviated Osteoarthritis through Piezo1/Calcineurin/NFAT1 Signaling Axis under Excessive Mechanical Strain.International journal of molecular sciences · 2023Article
- Systemic inflammation response index (SIRI) as a novel biomarker in patients with rheumatoid arthritis: a multi-center retrospective study.Clinical rheumatology · 2022Article
- PGC-1: a key regulator in bone homeostasis.Journal of bone and mineral metabolism · 2022Review
- CPT1A-Mediated Fatty Acid Oxidation Promotes Precursor Osteoclast Fusion in Rheumatoid Arthritis.Frontiers in immunology · 2022Article
- Gasdermin-E Mediated Pyroptosis-A Novel Mechanism Regulating Migration, Invasion and Release of Inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-like Synoviocytes.Frontiers in cell and developmental biology · 2021Article
- The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases.Frontiers in immunology · 2021Review
- Reduced skeletal muscle independently predicts 1-year aggravated joint destruction in patients with rheumatoid arthritis.Therapeutic advances in musculoskeletal disease · 2020Article
- [Simvastatin promotes murine osteoclasts apoptosisNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveActivation of osteoclastogenesis at the bone site in rheumatoid arthritis (RA) is well established. The mechanisms by which circulating osteoclast precursors contribute are still unclear. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is implicated in transcriptional regulation of osteoclastogenesis in mouse models. This study was undertaken to investigate the contribution of PGC-1β to circulating osteoclast precursors and its link to bone destruction in RA.
methodsPGC-1β expression in RA peripheral blood CD14+ monocytes was increased and showed correlation with joint destruction shown on radiographs. Cells from RA patients or healthy controls were transfected with a lentivirus vector for PGC-1β gene silencing or overexpression and cultured with macrophage colony-stimulating factor and RANKL. Bone resorption activity, bone-degrading enzymes, and signaling molecules were measured in these mature osteoclasts.
resultsIncreased nuclear accumulation of PGC-1β was observed in RA peripheral blood CD14+ monocytes, and these cells had stronger osteoclastogenesis than in healthy controls. PGC-1β protein expression was positively correlated with radiographic joint destruction (r = 0.396-0.413; all P < 0.05). PGC-1β knockdown suppressed (51-82% reduction) the expression of cathepsin K, tartrate-resistant acid phosphatase (TRAP), and matrix metalloproteinase 9 (MMP-9), as well as osteoclast differentiation and bone resorption activity. Conversely, PGC-1β overexpression increased these markers (by 1.5-1.8-fold) and osteoclastogenesis. VIVIT, an inhibitor of NFATc1 activation, inhibited the effect of overexpressed PGC-1β by reducing cathepsin K, TRAP, and MMP-9 expression. Chromatin immunoprecipitation assay and dual-luciferase reporter gene assay showed PGC-1β bound to NFATc1 promoter, leading to transcriptional activation.
conclusionActivation of the PGC-1β/NFATc1 pathway in circulating osteoclast precursors was associated with bone destruction in RA. This may represent a new treatment target.
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