ArticleJCI insight2023
Protein phosphatase PPM1A inhibition attenuates osteoarthritis via regulating TGF-β/Smad2 signaling in chondrocytes.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- From regeneration to immunomodulation: a 20-year global bibliometric analysis of platelet-rich plasma for osteoarthritis.Frontiers in medicine · 2026Pooled it
- Leptin promotes obesity‑related osteoarthritis progression via CD44/JAK2/STAT3 axis‑mediated chondrocyte apoptosis.Molecular medicine reports · 2026Article
- Artemotil Attenuates Fibrosis-Associated Chondrocyte Remodelling in Osteoarthritis in Association With STC1-Related TGF-β/SMAD2/3 Signalling.Journal of cellular and molecular medicine · 2026Article
- Article
- Inflaming and Immune-Resolving: The Ambivalent Role of Eosinophils in Osteoarthritis.International journal of molecular sciences · 2025Review
- Cuproptosis in osteoarthritis: Exploring chondrocyte cuproptosis and therapeutic avenues.Journal of orthopaedic translation · 2025Article
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Sodium Hyaluronate-PDGF Repairs Cartilage and Subchondral Bone Microenvironment via HIF-1α-VEGF-Notch and SDF-1-CXCR4 Inhibition in Osteoarthritis.Journal of cellular and molecular medicine · 2025Article
- Research progress of non-coding RNA regulating the role of PANoptosis in diabetes mellitus and its complications.Apoptosis : an international journal on programmed cell death · 2025Review
- A splicing-based multitissue association study of joint transcriptomes identified susceptibility genes for osteoarthritis.Frontiers in immunology · 2025Article
- Protein phosphatases regulate the formation of Müller glia-derived progenitor cells in the chick retina.Molecular and cellular neurosciences · 2024Article
- Protein phosphatases regulate the formation of Müller glia-derived progenitor cells in the chick retina.bioRxiv : the preprint server for biology · 2023Article
- Benzophenanthridine Alkaloid Chelerythrine Elicits Necroptosis of Gastric Cancer Cells via Selective Conjugation at the Redox Hyperreactive C-Terminal SecMolecules (Basel, Switzerland) · 2023Article
- PPM1A: TGFβ regulator and therapeutic target in OA.Nature reviews. Rheumatology · 2023Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β signaling is crucial for modulating osteoarthritis (OA), and protein phosphatase magnesium-dependent 1A (PPM1A) has been reported as a phosphatase of SMAD2 and regulates TGF-β signaling, while the role of PPM1A in cartilage homeostasis and OA development remains largely unexplored. In this study, we found increased PPM1A expression in OA chondrocytes and confirmed the interaction between PPM1A and phospho-SMAD2 (p-SMAD2). Importantly, our data show that PPM1A KO substantially protected mice treated with destabilization of medial meniscus (DMM) surgery against cartilage degeneration and subchondral sclerosis. Additionally, PPM1A ablation reduced the cartilage catabolism and cell apoptosis after the DMM operation. Moreover, p-SMAD2 expression in chondrocytes from KO mice was higher than that in WT controls with DMM induction. However, intraarticular injection with SD-208, repressing TGF-β/SMAD2 signaling, dramatically abolished protective phenotypes in PPM1A-KO mice. Finally, a specific pharmacologic PPM1A inhibitor, Sanguinarine chloride (SC) or BC-21, was able to ameliorate OA severity in C57BL/6J mice. In summary, our study identified PPM1A as a pivotal regulator of cartilage homeostasis and demonstrated that PPM1A inhibition attenuates OA progression via regulating TGF-β/SMAD2 signaling in chondrocytes and provided PPM1A as a potential target for OA treatment.
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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.