ArticleArthritis research & therapy2015
p21 deficiency is susceptible to osteoarthritis through STAT3 phosphorylation.
Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Standardized Effect Measures Informing Next-Generation Strategies for Mechanical Stimulation in Cartilage Tissue Engineering.Advanced healthcare materials · 2026Pooled it
- Cyclin-dependent kinase inhibitor-1 deficiency enhances bone destruction in a mouse model of arthritis.Bone reports · 2025Article
- Key Role of STAT3 in Osteoarthritis: From Pathogenic Mechanisms to Targeted Therapy.International journal of nanomedicine · 2025Review
- Article
- Relation of STAT3 rs1053005 Variation and miR-452-3p with Osteoarthritis Susceptibility and Severity and the Clinical Response to High-Molecular-Weight Hyaluronic Acid Injection in Osteoarthritis Patients.Diagnostics (Basel, Switzerland) · 2023Article
- Knockdown of LINC01138 protects human chondrocytes against IL-1β-induced damage by regulating the hsa-miR-1207-5p/KIAA0101 axis.Immunity, inflammation and disease · 2023Article
- LncRNA TUG regulates osteogenic differentiation of bone marrow mesenchymal stem cells via miRNA-204/SIRT 1.Journal of musculoskeletal & neuronal interactions · 2022Article
- Arctiin-reinforced antioxidant microcarrier antagonizes osteoarthritis progression.Journal of nanobiotechnology · 2022Article
- p21Cartilage · 2021Article
- Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation.Scientific reports · 2021Article
- The immunoregulatory role of p21 in the development of the temporomandibular joint-osteoarthritis.Clinical and experimental dental research · 2021Article
- Lycopene inhibits IL-1β-induced inflammation in mouse chondrocytes and mediates murine osteoarthritis.Journal of cellular and molecular medicine · 2021Article
- lncRNA SNHG16 promotes the occurrence of osteoarthritis by sponging miR‑373‑3p.Molecular medicine reports · 2021Article
- Selective STAT3 Inhibitor Alantolactone Ameliorates OsteoarthritisFrontiers in pharmacology · 2021Article
- Silencing of TLR7 protects against lipopolysaccharide-induced chondrocyte apoptosis and injury by blocking the p21-mediated JAK2/STAT3 pathway.American journal of translational research · 2021Article
- Beneficial effects ofFood science & nutrition · 2020Article
- Kruppel-like factor 4 upregulates matrix metalloproteinase 13 expression in chondrocytes via mRNA stabilization.Cell and tissue research · 2020Article
- Parathyroid hormone (1-34) ameliorates cartilage degeneration and subchondral bone deterioration in collagenase-induced osteoarthritis model in mice.Bone & joint research · 2020Article
- Understanding cartilage protection in OA and injury: a spectrum of possibilities.BMC musculoskeletal disorders · 2020Review
- γ-Mangostin isolated fromAging · 2020Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionOsteoarthritis (OA) is a multifactorial disease, and recent studies have suggested that cell cycle-related proteins play a role in OA pathology. p21 was initially identified as a potent inhibitor of cell cycle progression. However, it has been proposed that p21 is a regulator of transcription factor activity. In this study, we evaluated the role of p21 in response to biomechanical stress.
methodsHuman chondrocytes were treated with p21-specific small interfering RNA (siRNA), and cyclic tensile strain was introduced in the presence or absence of a signal transducer and activator of transcription 3 (STAT3)-specific inhibitor. Further, we developed an in vivo OA model in a p21-knockout background for in vivo experiments.
resultsThe expression of matrix metalloproteinase (MMP13) mRNA increased in response to cyclic tensile strain following transfection with p21 siRNA, whereas the expression of aggrecan was decreased. Phospho-STAT3 and MMP-13 protein levels increased following downregulation of p21, and this was reversed by treatment with a STAT3 inhibitor. p21-deficient mice were susceptible to OA, and this was associated with increased STAT3 phosphorylation, elevated MMP-13 expression, and elevation of synovial inflammation. The expression of p21 mRNA was decreased and phosphorylation of STAT3 was elevated in human OA chondrocytes.
conclusionsThe lack of p21 has catabolic effects by regulation of aggrecan and MMP-13 expression through STAT3 phosphorylation in the cartilage tissue. p21 may function as a regulator of transcriptional factors other than the inhibitor of cell cycle progression in the cartilage tissue. Thus, the regulation of p21 may be a therapeutic strategy for the treatment of OA.
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