ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2018
Phlpp inhibitors block pain and cartilage degradation associated with osteoarthritis.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Structural and functional changes in articulating joints during aging of male and female C57BL/6JN mice.Osteoarthritis and cartilage · 2026Article
- A Review of Rodent Behavior, Mobility, and Pain Modifications in Response to Destabilization of the Medial Meniscus Injury.Biomedicines · 2025Review
- Article
- Postnatal deletion of Phlpp1 in chondrocytes delays post-traumatic osteoarthritis in male mice.Osteoarthritis and cartilage open · 2025Article
- Longitudinal assessment of structural and locomotor deficits as a prediction of severity in the collagenase-induced mouse model of osteoarthritis.Arthritis research & therapy · 2025Article
- Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.Bone · 2024Article
- MiR203a-3p as a potential biomarker for synovial pathology associated with osteoarthritis: a pilot study.Journal of orthopaedic surgery and research · 2024Article
- Mechanism study of BMSC-exosomes combined with hyaluronic acid gel in the treatment of posttraumatic osteoarthritis.Heliyon · 2024Article
- Inhibition of Phlpp1 preserves the mechanical integrity of articular cartilage in a murine model of post-traumatic osteoarthritis.Osteoarthritis and cartilage · 2024Article
- Recent Advances in Small Molecule Inhibitors for the Treatment of Osteoarthritis.Journal of clinical medicine · 2023Review
- Article
- PHLPP Inhibitor NSC74429 Is Neuroprotective in Rodent Models of Cardiac Arrest and Traumatic Brain Injury.Biomolecules · 2022Article
- PHLPP Signaling in Immune Cells.Current topics in microbiology and immunology · 2022Review
- Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs.Cellular and molecular life sciences : CMLS · 2021Review
- Chondrocytic and pharmacokinetic properties of Phlpp inhibitors.Osteoarthritis and cartilage open · 2021Article
- Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes.Cell reports · 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 balance: restoration of protein kinase C in cancer.The Biochemical journal · 2021Review
- The Regenerative Horizon: Opportunities for Nursing Research and Practice.Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing · 2019Article
- Phlpp1 is associated with human intervertebral disc degeneration and its deficiency promotes healing after needle puncture injury in mice.Cell death & disease · 2019Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Phlpp protein phosphatases are abnormally abundant within human osteoarthritic articular chondrocytes and may contribute to the development of osteoarthritis. Mice lacking Phlpp1 were previously shown to be resistant to post-traumatic osteoarthritis. Here a small molecule with therapeutic properties that inhibits Phlpp1 and Phlpp2 was tested for its ability to slow post-traumatic OA in mice and to stimulate anabolic pathways in human articular cartilage from OA joints. PTOA was induced in male C57Bl/6 mice by surgically destabilizing the meniscus. Seven weeks after surgery, mice received a single intra-articular injection of the Phlpp inhibitor NSC117079 or saline. Mechanical allodynia was measured with von Frey assays, mobility was tracked in an open field system, and cartilage damage was assessed histologically. A single intra-articular injection of the Phlpp inhibitor NSC117079 attenuated mechanical allodynia and slowed articular cartilage degradation in joints with a destabilized meniscus. Animals treated with the Phlpp inhibitor 7 weeks after injury maintained normal activity levels, while those in the control group traveled shorter distances and were less active 3 months after the joint injury. NSC117079 also increased production of cartilage extracellular matrix components (glycosaminoglycans and aggrecan) in over 90% of human articular cartilage explants from OA patients and increased phosphorylation of Phlpp1 substrates (AKT2, ERK1/2, and PKC) in human articular chondrocytes. Our results indicate that Phlpp inhibitor NSC117079 is a novel osteoarthritis disease modifying drug candidate that may have palliative affects. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1487-1497, 2018.
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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 OpenQuestion graph.