ArticleJCI insight2020
Arp2/3 inactivation causes intervertebral disc and cartilage degeneration with dysregulated TonEBP-mediated osmoadaptation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Human hip osteoarthritis-associatedbioRxiv : the preprint server for biology · 2026Article
- Loss of MCT1 mediated lactate uptake causes delayed endplate maturation and intervertebral disc degeneration.Cell death & disease · 2026Article
- Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice.Bone research · 2026Article
- Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice.Research square · 2025Article
- Sirt6 deficiency promotes senescence and age-associated intervertebral disc degeneration in mice.Bone research · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Increased HIF-2α activity in the nucleus pulposus causes intervertebral disc degeneration in the aging mouse spine.Frontiers in cell and developmental biology · 2024Article
- Loss of function mutation in Ank causes aberrant mineralization and acquisition of osteoblast-like-phenotype by the cells of the intervertebral disc.Cell death & disease · 2023Article
- Article
- The Chemistry and Biology of Collagen Hybridization.Journal of the American Chemical Society · 2023Review
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- Proteomic profiling of extracellular vesicles in synovial fluid and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients reveals novel immunopathogenic biomarkers.Frontiers in immunology · 2023Article
- Conditional Deletion of HIF-2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age-Dependent Structural Changes in Intervertebral Disc.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Dermcidin Enhances the Migration, Invasion, and Metastasis of Hepatocellular Carcinoma CellsJournal of clinical and translational hepatology · 2022Article
- The cGAS-STING Pathway Affects Vertebral Bone but Does Not Promote Intervertebral Disc Cell Senescence or Degeneration.Frontiers in immunology · 2022Article
- The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.Frontiers in immunology · 2022Review
- Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies.Expert reviews in molecular medicine · 2021Review
- Article
- Role of autophagy in intervertebral disc and cartilage function: implications in health and disease.Matrix biology : journal of the International Society for Matrix Biology · 2021Review
- Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function.International journal of molecular sciences · 2021Review
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Extracellular matrix and osmolarity influence the development and homeostasis of skeletal tissues through Rho GTPase-mediated alteration of the actin cytoskeleton. This study investigated whether the actin-branching Arp2/3 complex, a downstream effector of the Rho GTPases Cdc42 and Rac1, plays a critical role in maintaining the health of matrix-rich and osmotically loaded intervertebral discs and cartilage. Mice with constitutive intervertebral disc- and cartilage-specific deletion of the critical Arp2/3 subunit Arpc2 (Col2-Cre; Arpc2fl/fl) developed chondrodysplasia and spinal defects. Since these mice did not survive to adulthood, we generated mice with inducible Arpc2 deletion in disc and cartilage (Acan-CreERT2; Arpc2fl/fl). Inactivation of Arp2/3 at skeletal maturity resulted in growth plate closure, loss of proteoglycan content in articular cartilage, and degenerative changes in the intervertebral disc at 1 year of age. Chondrocytes with Arpc2 deletion showed compromised cell spreading on both collagen and fibronectin. Pharmacological inhibition of Cdc42 and Arp2/3 prevented the osmoadaptive transcription factor TonEBP/NFAT5 from recruiting cofactors in response to a hyperosmolarity challenge. Together, these findings suggest that Arp2/3 plays a critical role in cartilaginous tissues through the regulation of cell-extracellular matrix interactions and modulation of TonEBP-mediated osmoadaptation.
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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.