ArticleOsteoarthritis and cartilage2016
Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis.
Article in Osteoarthritis and cartilage, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- PHLPP1 Regulates Inflammatory Signaling in Degenerated Nucleus Pulposus Cells in Mice and Humans.Cells · 2026Article
- Postnatal deletion of Phlpp1 in chondrocytes delays post-traumatic osteoarthritis in male mice.Osteoarthritis and cartilage open · 2025Article
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.Bone · 2024Article
- Alterations in DNA methylation machinery in a rat model of osteoarthritis of the hip.Journal of orthopaedic surgery and research · 2024Article
- Inhibition of Phlpp1 preserves the mechanical integrity of articular cartilage in a murine model of post-traumatic osteoarthritis.Osteoarthritis and cartilage · 2024Article
- Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health.JOR spine · 2024Article
- Article
- The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis.International journal of molecular sciences · 2023Review
- The epigenetic players and the chromatin marks involved in the articular cartilage during osteoarthritis.Frontiers in physiology · 2023Review
- Article
- PHLPP Signaling in Immune Cells.Current topics in microbiology and immunology · 2022Review
- On the PHLPPside: Emerging roles of PHLPP phosphatases in the heart.Cellular signalling · 2021Review
- Chondrocytic and pharmacokinetic properties of Phlpp inhibitors.Osteoarthritis and cartilage open · 2021Article
- Pleckstrin homology (PH) domain and Leucine Rich Repeat Phosphatase 1 (Phlpp1) Suppresses Parathyroid Hormone Receptor 1 (Pth1r) Expression and Signaling During Bone Growth.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling.Annual review of pharmacology and toxicology · 2021Review
- Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications.Frontiers in cell and developmental biology · 2021Review
- Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling.Science advances · 2020Article
- Phlpp1 is associated with human intervertebral disc degeneration and its deficiency promotes healing after needle puncture injury in mice.Cell death & disease · 2019Article
- DNA methylation and FoxO3a regulate PHLPP1 expression in chondrocytes.Journal of cellular biochemistry · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveOsteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. OA is characterized by articular chondrocyte deterioration, subchondral bone changes and debilitating pain. One strategy to promote cartilage regeneration and repair is to accelerate proliferation and matrix production of articular chondrocytes. We previously reported that the protein phosphatase Phlpp1 controls chondrocyte differentiation by regulating the activities of anabolic kinases. Here we examined the role of Phlpp1 in OA progression in a murine model. We also assessed PHLPP1 expression and promoter methylation.
designKnee joints of WT and Phlpp1(-/-) mice were surgically destabilized by transection of the medial meniscal ligament (DMM). Mice were assessed for signs of OA progression via radiographic and histological analyses, and pain assessment for mechanical hypersensitivity using the von Frey assay. Methylation of the PHLPP1 promoter and PHLPP1 expression were evaluated in human articular cartilage and chondrocyte cell lines.
resultsFollowing DMM surgeries, Phlpp1 deficient mice showed fewer signs of OA and cartilage degeneration. Mechanical allodynia associated with DMM surgeries was also attenuated in Phlpp1(-/-) mice. PHLPP1 was highly expressed in human articular cartilage from OA patients, but was undetectable in cartilage specimens from femoral neck fractures (FNFxs). Higher PHLPP1 levels correlated with less PHLPP1 promoter CpG methylation in cartilage from OA patients. Blocking cytosine methylation or treatment with inflammatory mediators enhanced PHLPP1 expression in human chondrocyte cell lines.
conclusionPhlpp1 deficiency protects against OA progression while CpG demethylation and inflammatory cytokines promote PHLPP1 expression.
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