ArticleInternational journal of molecular sciences2019
Lysyl Oxidase-Like 2 Protects against Progressive and Aging Related Knee Joint Osteoarthritis in Mice.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- LOXL2 deletion triggers TMJ osteoarthritis, while overexpression protects it from NF-κB-induced chondrocyte apoptosis.International journal of oral science · 2026Article
- LOXL2 alleviates post-traumatic knee osteoarthritis and pain.Journal of orthopaedic translation · 2025Article
- ROS-degradable hydrogel delivering LOXL2-LNPs rescues disc degeneration by synchronously suppressing cellular senescence and oxidative damage.Journal of nanobiotechnology · 2025Article
- A multi-tissue human knee single-cell atlas identifies that osteoarthritis reduces regenerative tissue stem cells while increasing inflammatory pain macrophages.Communications biology · 2025Article
- Damage of the Bone Marrow Stromal Precursors in Patients with Acute Leukemia at the Onset of the Disease and During Treatment.International journal of molecular sciences · 2024Article
- Spinosin ameliorates osteoarthritis through enhancing the Nrf2/HO-1 signaling pathway.European journal of histochemistry : EJH · 2024Article
- Lysyl oxidase like-2 in fibrosis and cardiovascular disease.American journal of physiology. Cell physiology · 2023Review
- Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review.Frontiers in medicine · 2023Article
- Loxl3 Promotes Melanoma Progression and Dissemination Influencing Cell Plasticity and Survival.Cancers · 2022Article
- Stigmasterol alleviates interleukin-1beta-induced chondrocyte injury by down-regulatingsterol regulatory element binding transcription factor 2 to regulateferroptosis.Bioengineered · 2021Article
- The Expression Patterns and Roles of Lysyl Oxidases in Aortic Dissection.Frontiers in cardiovascular medicine · 2021Article
- LOXL2 promotes aggrecan and gender-specific anabolic differences to TMJ cartilage.Scientific reports · 2020Article
- Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice.International journal of molecular sciences · 2020Article
- Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation.Frontiers in bioengineering and biotechnology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe goal of this study was to determine if adenovirus-delivered LOXL2 protects against progressive knee osteoarthritis (OA), assess its specific mechanism of action; and determine if the overexpression of LOXL2 in transgenic mice can protect against the development of OA-related cartilage damage and joint disability.
methodsFour-month-old Cho/+ male and female mice were intraperitoneally injected with either Adv-RFP-LOXL2 or an empty vector twice a month for four months. The proteoglycan levels and the expression of anabolic and catabolic genes were examined by immunostaining and qRT-PCR. The effect of LOXL2 expression on signaling was tested via the pro-inflammatory cytokine IL1β in the cartilage cell line ATDC5. Finally; the OA by monosodium iodoacetate (MIA) injection was also induced in transgenic mice with systemic overexpression of LOXL2 and examined gene expression and joint function by treadmill tests and assessment of allodynia.
resultsThe adenovirus treatment upregulated LOXL2; Sox9; Acan and Runx2 expression in both males and females. The Adv-RFP-LOXL2 injection; but not the empty vector injection increased proteoglycan staining and aggrecan expression but reduced MMP13 expression. LOXL2 attenuated IL-1β-induced phospho-NF-κB/p65 and rescued chondrogenic lineage-related genes in ATDC5 cells; demonstrating one potential protective mechanism. LOXL2 attenuated phospho-NF-κB independent of its enzymatic activity. Finally; LOXL2-overexpressing transgenic mice were protected from MIA-induced OA-related functional changes; including the time and distance traveled on the treadmill and allodynia.
conclusionOur study demonstrates that systemic LOXL2 adenovirus or LOXL2 genetic overexpression in mice can protect against OA. These findings demonstrate the potential for LOXL2 gene therapy for knee-OA clinical treatment in the future.
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Registered trials
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