ArticleInternational journal of molecular sciences2021
High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- Refractory Stasis Dermatitis Due to Chronic Venous Insufficiency With Psychosocial Worsening in 2 Septuagenarian Patients Treated With Hyaluronic Acid-Succinic Acid Intradermotherapy.The American journal of case reports · 2026Article
- An analysis of the cytokine profile of platelet-rich plasma when combined in vitro with low versus high molecular weight hyaluronic acid.Bone & joint research · 2026Article
- Effects of Intra-Articular Administration of High-Molecular-Weight Linear Hyaluronic Acid on Synovial Fluid Characteristics and Joint Environment.Antioxidants (Basel, Switzerland) · 2026Article
- Paradigm shift in macrophage polarization in osteoarthritis: from M1/M2 imbalance to macrophage state reprogramming in the ageing immune microenvironment.Frontiers in immunology · 2026Review
- Impact of Symptomatic Slow-Acting Drugs on Inflammatory Pathways in Osteoarthritis: Therapeutic Advances and Future Challenges.ACS pharmacology & translational science · 2025Review
- Macrophages: pivotal orchestrators and emerging therapeutic targets in osteoarthritis pathogenesis.Journal of translational medicine · 2025Review
- Review
- Cooperative Interaction of Hyaluronic Acid with Epigallocatechin-3-O-gallate and Xanthohumol in Targeting the NF-κB Signaling Pathway in a Cellular Model of Rheumatoid Arthritis.Antioxidants (Basel, Switzerland) · 2025Article
- Hand Osteoarthritis: Molecular Mechanisms, Randomized Controlled Trials, and the Future of Targeted Treatment.International journal of molecular sciences · 2025Review
- Heat shock proteins in osteoarthritis: molecular mechanisms, pathogenic roles, and therapeutic opportunities.Frontiers in immunology · 2025Review
- Research progress on damage-associated molecular patterns in acute kidney injury.Frontiers in immunology · 2025Review
- Role of oral hyaluronic acid for joint health: insights from rat models and clinical trials.Frontiers in nutrition · 2025Article
- Article
- Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage.International journal of molecular sciences · 2024Review
- Puerarin inhibits Staphylococcus aureus-induced endometritis through attenuating inflammation and ferroptosis via regulating the P2X7/NLRP3 signalling pathway.Journal of cellular and molecular medicine · 2024Article
- Hyaluronic Acid Viscosupplement Modulates Inflammatory Mediators in Chondrocyte and Macrophage Coculture via MAPK and NF-κB Signaling Pathways.ACS omega · 2024Article
- Role of crosstalk between synovial cells and chondrocytes in osteoarthritis (Review).Experimental and therapeutic medicine · 2024Review
- Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.Respiratory research · 2024Article
- Pain Management Strategies in Osteoarthritis.Biomedicines · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1β to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1β increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.
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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 Socratic graph.