ArticleNature communications2024
A RANKL-UCHL1-sCD13 negative feedback loop limits osteoclastogenesis in subchondral bone to prevent osteoarthritis progression.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- From pathogenic to reparative: Context-Dependent function of extracellular vesicles in osteoarthritis.Bioactive materials · 2027Review
- Anti-RANKL antibody treatment mitigates subchondral bone loss and cartilage degeneration without affecting synovial inflammation in a mouse model of rotator cuff tear arthropathy.Bone & joint research · 2026Article
- The Emerging Role of UCHL1 in Neurological and Musculoskeletal Diseases.Immunology and cell biology · 2026Review
- Therapeutic effects of Tetramethylpyrazine on Cartilage in Rat Model of Post-traumatic Osteoarthritis.Regenerative therapy · 2026Article
- Application and prospects of nanomaterials in osteoporosis treatment.International journal of pharmaceutics: X · 2026Review
- Osteoclast Heterogeneity in Osteoarthritis: From Single-Cell Microenvironments to Program-Specific Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Dapagliflozin regulates chondrocyte homeostasis and protects against osteoarthritis via targets AMPKα and SGLT2.Cell death discovery · 2026Article
- Research Progress on Dance Training as a Mechanical Stimulus for the Prevention and Treatment of Osteoporosis: A Narrative Review.International journal of molecular sciences · 2026Review
- Targeted Inhibition of CD74Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association between the cartilage volume and bone mineral density in symptomatic knee osteoarthritis and the mediating role of bone mineral content.BMC musculoskeletal disorders · 2026Article
- Effect of distraction length on the morphology of knee cartilage in a rat model of femoral distraction osteogenesis.Frontiers in physiology · 2026Article
- Targeting subchondral osteoporosis in osteoarthritis: biomechanical crosstalk and the therapeutic rationale for inflammatory microenvironment remodeling.Frontiers in immunology · 2026Review
- CORO1A links inflammatory chondrocyte subpopulations to immune microenvironment alterations in osteoarthritis: an integrative multi-omics and single-cell study.Frontiers in immunology · 2026Article
- Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives.Theranostics · 2026Review
- Targeting the osteoimmune microenvironment to prevent regulated chondrocyte death in osteoarthritis: therapeutic potential of natural products.Frontiers in cell and developmental biology · 2026Review
- New therapeutic target for osteoarthritis: modulating immune-metabolic aberrations and micromilieu remodeling in underlying bone.Frontiers in pharmacology · 2026Review
- Targeting Osteoclastogenesis: Sabutoclax reduces tumor-associated osteolysis and tumor burden within the bone microenvironment.American journal of cancer research · 2026Article
- Article
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA.
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