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An in vivo cross-linkable hyaluronan gel with inherent anti-inflammatory properties reduces OA cartilage destruction in female mice subjected to cruciate ligament transection
- Source :
- Osteoarthritis and cartilage. 25(1)
- Publication Year :
- 2016
-
Abstract
- Summary Objective To explore the possibility of cartilage protection in osteoarthritis (OA) by intraarticular injection of a chemically modified hyaluronan (HA) gel and investigate whether the chemical modifications provide intrinsic anti-inflammatory activity. Method OA was induced in C57BL/6 mice by anterior cruciate ligament transection (ACLT) and HA gel or carbazate-modified component was injected intra-articularly. Assessment of cartilage rescue was performed by histology, immunohistochemistry and TUNEL analysis. Serum levels of proinflammatory cytokines were evaluated with cytometric bead array, measuring IL-1β, TNF, IFN-γ, KC/CXCL1 and MCP-1. Results Intraarticular injection of the HA gel showed significantly reduced cartilage destruction and decreased osteophyte formation. Besides the biological and biomechanical effects of HA, we investigated lipid peroxidation products as an alternative inflammatory and potential mechanism contributing to OA. To address this, injection of the carbazate-modified component alone was performed, which also demonstrated a cartilage-saving effect. Besides the cartilage amelioration effects, decreased apoptosis, 4-hydroxynonenal (4-HNE) and MHC class II staining was recorded. No changes in serum levels of proinflammatory cytokines were detected. Conclusion We have shown that the HA gel has an anti-destructive effect on articular cartilage (AC). Our results demonstrated that the carbazate-modified component could suppress apoptotic events, potentially by quenching of ROS/LPO products such as 4-HNE in OA joints. Modification of the HA molecule offers opportunities to introduce (covalent) coupling of additional molecules to the gel, with controlled retention and subsequent release in the joint.
- Subjects :
- 0301 basic medicine
Cartilage, Articular
Anterior cruciate ligament
Biomedical Engineering
Anti-Inflammatory Agents
Osteoarthritis
Proinflammatory cytokine
Lipid peroxidation
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Rheumatology
In vivo
medicine
Animals
Orthopedics and Sports Medicine
Anterior Cruciate Ligament
Hyaluronic Acid
030203 arthritis & rheumatology
TUNEL assay
Cartilage
Anterior Cruciate Ligament Injuries
medicine.disease
Molecular biology
Hindlimb
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
chemistry
Apoptosis
Immunology
Female
Gels
Subjects
Details
- ISSN :
- 15229653
- Volume :
- 25
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Osteoarthritis and cartilage
- Accession number :
- edsair.doi.dedup.....7edf358ab54835a4713aba23af3b0028