ArticleBone research2024
Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis.
Article in Bone research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Spatial multi‑omics identifies an SPP1+ macrophage‑driven anti‑apoptotic niche in osteoarthritis synovium via the SPP1‑CD44 axis.International journal of molecular medicine · 2026Article
- Smart Nanodelivery Systems for Immunometabolic Modulation in Osteoarthritis.Exploration (Beijing, China) · 2026Review
- Polymeric Gene Delivery at Sub-Stoichiometric N/P Ratios.Polymer science & technology (Washington, D.C.) · 2026Article
- Chitinase-like proteins de-N-glycosylating CD36 modify cholesterol metabolism in atherosclerotic macrophages.Nature communications · 2026Article
- Cigarette Smoke Extract Alters the Inflammatory Secretome of Osteoarthritis-Affected Synovium Increasing Joint Tissue Oxidative Stress in an Indirect Co-Culture Model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Targeted knockdown of Piezo1 in synovial macrophages attenuates osteoarthritis development.Journal of orthopaedic translation · 2026Article
- Synovial inflammatory macrophage-derived extracellular vesicles exacerbate cartilage lesions with a FMRP-selectively sorted manner in osteoarthritis.Bone research · 2026Article
- Exosomes: critical mediator and therapeutic target for osteoarthritis.American journal of translational research · 2026Review
- Remodeling of senescent macrophages in synovium alleviates trauma- and aging-induced osteoarthritis.Bioactive materials · 2026Article
- How Selective are Nanomaterials to Treat Osteoarthritis.International journal of nanomedicine · 2026Review
- Intra-Articular Delivery of Nanoemulsified Curcumin Ameliorates Joint Degeneration in a Chemically Induced Model of Osteoarthritis.International journal of molecular sciences · 2025Article
- Omentin-1 reduced synovial M1 macrophages through SIRT6 signaling pathway and alleviated knee osteoarthritis response in mice.Arthritis research & therapy · 2025Article
- Aging microenvironment in osteoarthritis focusing on early-stage alterations and targeted therapies.Bone research · 2025Review
- Fire needling acupuncture attenuates synovial inflammation and cartilage degeneration in knee osteoarthritis via SDF-1/CXCR4-mediated macrophage polarization.Clinical rheumatology · 2025Article
- Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments.Signal transduction and targeted therapy · 2025Review
- The dual role of PGAM5 in inflammation.Experimental & molecular medicine · 2025Review
- Immunological mechanisms in steroid-induced osteonecrosis of the femoral head.Frontiers in immunology · 2025Review
- Mitochondrial metabolic regulation of macrophage polarization in osteomyelitis and other orthopedic disorders: mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Osteoimmunology in Osteoarthritis: Unraveling the Interplay of Immunity, Inflammation, and Joint Degeneration.Journal of inflammation research · 2025Review
- SLC40A1-mediated positive feedback loop with M1 macrophages suppresses epithelial ovarian cancer progression.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of β-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and β-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.
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Registered trials
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.