ArticleJournal of inflammation research2021
Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis.
Article in Journal of inflammation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Acid-sensing ion channels in the vasculature: emerging roles in systemic and pulmonary circulations.Pflugers Archiv : European journal of physiology · 2026Review
- Sex hormones and their receptors in osteoarthritis: current research progress.Annals of joint · 2026Review
- Mitochondrial proteomics reveals the impact of Estrogen in enhancing energy metabolism of patient-derived fibroblast-like synoviocytes in rheumatoid arthritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Synovial fibroblast derived small extracellular vesicles miRNA15-29148 promotes articular chondrocyte apoptosis in rheumatoid arthritis.Bone research · 2025Article
- Steroid hormones and influence of therapeutic drugs in Chinese postmenopausal rheumatoid arthritis patients.Frontiers in immunology · 2025Article
- Joint Inflammation Correlates with Joint GPR30 Expression in Males and Hippocampal GPR30 Expression in Females in a Rat Model of Rheumatoid Arthritis.International journal of molecular sciences · 2024Article
- The Loss of Estradiol by Androgen Deprivation in Prostate Cancer Patients Shows the Importance of Estrogens in Males.Journal of the Endocrine Society · 2024Review
- Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention.Cell death discovery · 2023Review
- Low back pain and osteoarthritis pain: a perspective of estrogen.Bone research · 2023Review
- Sex-dependent variation in cartilage adaptation: from degeneration to regeneration.Biology of sex differences · 2023Review
- Estrogen antagonizes ASIC1a-induced chondrocyte mitochondrial stress in rheumatoid arthritis.Journal of translational medicine · 2022Article
- Instructive cartilage regeneration modalities with advanced therapeutic implantations under abnormal conditions.Bioactive materials · 2022Review
- Yi Shen Juan Bi Pill alleviates bone destruction in inflammatory arthritis under postmenopausal conditions by regulating ephrinB2 signaling.Frontiers in pharmacology · 2022Article
- DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology.Frontiers in immunology · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe severity of rheumatoid arthritis (RA) in women is generally lower than that in men. RA is mediated, at least in part, by the protective effects of estradiol. However, the mechanisms underlying the protective effect of estradiol on RA are still unclear. Recent studies have demonstrated that activation of acid-sensing ion channel 1a (ASIC1a) by tissue acidosis plays an important role in the injury of cartilage in RA. Here, we assessed the effects of estradiol on acid-mediated cartilage injury both in vitro and in vivo and explored the involvement of ASIC1a in RA and its underlying mechanism.
methodsCultured primary articular chondrocytes were subjected to acidosis-mediated injury in vitro. Beclin1, LC3, p62, GPER1, and ASIC1a expression was detected through Western blotting, quantitative real-time PCR, and immunofluorescence analysis. Adjuvant arthritis (AA) was induced in rats through intradermal immunization by injecting 0.25 mL heat-killed mycobacteria (10 mg/mL) suspended in complete Freund's adjuvant into the left hind metatarsal footpad. The levels of estrogen and related inflammatory factors in the serum were measured using enzyme-linked immunosorbent assay. The expression of ASIC1a and autophagy-related proteins was detected through immunohistochemical analysis and Western blot.
resultsTreatment of primary articular chondrocytes with estradiol decreased the expression of ASIC1a and autophagy level. The symptoms of cartilage damage and levels of inflammatory cytokines in the serum were reduced after estradiol treatment in the rats with AA. In addition, estradiol treatment reduced ASIC1a expression via the PI3K-AKT-mTOR pathway, among which G-protein coupled estradiol receptor 1 (GPER1) plays a regulatory role. Finally, the level of autophagy in chondrocytes was decreased by the selective ASIC1a blocker psalmotoxin-1 (PCTX-1).
conclusionEstradiol can protect the cartilage of rats with AA against acidosis-mediated damage and autophagy by suppressing ASIC1a expression through GPER1.
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