ArticleArthritis and rheumatism2010
Matrix metalloproteinase 13 loss associated with impaired extracellular matrix remodeling disrupts chondrocyte differentiation by concerted effects on multiple regulatory factors.
Article in Arthritis and rheumatism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- A Modular Bioinstructive Platform Reveals Mechanistic Insights into Additive-Free, Topography-Driven Osteogenesis.Advanced healthcare materials · 2026Article
- Anabolic indices of matrix proteins identify regenerative small RNA intrinsic to human cartilage.Science advances · 2025Article
- Deciphering cartilage neuro-immune interactions and innervation profile through 3D engineered osteoarthritic micropathophysiological system.Materials today. Bio · 2025Article
- Cartilage tissue engineering using decellularized biomatrix hydrogel containing TGF-β-loaded alginate microspheres in mechanically loaded bioreactor.Scientific reports · 2024Article
- The Reparative Function of MMP13 in Tertiary Reactionary Dentinogenesis after Tooth Injury.International journal of molecular sciences · 2024Article
- Hypoxia Preconditioned Serum (HPS) Promotes Proliferation and Chondrogenic Phenotype of Chondrocytes In Vitro.International journal of molecular sciences · 2023Article
- Collagen-Derived Dipeptide Pro-Hyp Enhanced ATDC5 Chondrocyte Differentiation under Hypoxic Conditions.Molecules (Basel, Switzerland) · 2023Article
- NOTCH1: A Novel Player in the Molecular Crosstalk Underlying Articular Chondrocyte Protection by Oleuropein and Hydroxytyrosol.International journal of molecular sciences · 2023Article
- Article
- Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes.International journal of molecular sciences · 2021Article
- Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases.Scientific reports · 2021Article
- Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthritis.Experimental and therapeutic medicine · 2021Article
- CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation.Life science alliance · 2019Article
- Redifferentiation of Articular Chondrocytes by Hyperacute Serum and Platelet Rich Plasma in Collagen Type I Hydrogels.International journal of molecular sciences · 2019Article
- Biochemical and Mechanical Gradients Synergize To Enhance Cartilage Zonal Organization in 3D.ACS biomaterials science & engineering · 2018Article
- Cellular and molecular changes to chondrocytes in an in vitro model of developmental dysplasia of the hip‑an experimental model of DDH with swaddling position.Molecular medicine reports · 2018Article
- PKR activation causes inflammation and MMP-13 secretion in human degenerated articular chondrocytes.Redox biology · 2018Article
- Recent Insights into the Contribution of the Changing Hypertrophic Chondrocyte Phenotype in the Development and Progression of Osteoarthritis.Frontiers in bioengineering and biotechnology · 2018Review
- Glycogen Synthase Kinase-3β Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.Scientific reports · 2017Article
- Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration.Biomaterials · 2017Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveTo link matrix metalloproteinase 13 (MMP-13) activity and extracellular matrix (ECM) remodeling to alterations in regulatory factors leading to a disruption in chondrocyte homeostasis.
methodsMMP-13 expression was ablated in primary human chondrocytes by stable retrotransduction of short hairpin RNA. The effects of MMP-13 knockdown on key regulators of chondrocyte differentiation (SOX9, runt-related transcription factor 2 [RUNX-2], and beta-catenin) and angiogenesis (vascular endothelial growth factor [VEGF]) were scored at the protein level (by immunohistochemical or Western blot analysis) and RNA level (by real-time polymerase chain reaction) in high-density monolayer and micromass cultures under mineralizing conditions. Effects on cellular viability in conjunction with chondrocyte progression toward a hypertrophic-like state were assessed in micromass cultures. Alterations in SOX9 subcellular distribution were assessed using confocal microscopy in micromass cultures and also in osteoarthritic cartilage.
resultsDifferentiation of control chondrocyte micromasses progressed up to a terminal phase, with calcium deposition in conjunction with reduced cell viability and scant ECM. MMP-13 knockdown impaired ECM remodeling and suppressed differentiation in conjunction with reduced levels of RUNX-2, beta-catenin, and VEGF. MMP-13 levels in vitro and ECM remodeling in vitro and in vivo were linked to changes in SOX9 subcellular localization. SOX9 was largely excluded from the nuclei of chondrocytes with MMP-13-remodeled or -degraded ECM, and exhibited an intranuclear staining pattern in chondrocytes with impaired MMP-13 activity in vitro or with more intact ECM in vivo.
conclusionMMP-13 loss leads to a breakdown in primary human articular chondrocyte differentiation by altering the expression of multiple regulatory factors.
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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.