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Early supplemental α2‐macroglobulin attenuates cartilage and bone damage by inhibiting inflammation in collagen II‐induced arthritis model
- Source :
- International Journal of Rheumatic Diseases. 22:654-665
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Objective To determine if early supplemental intra-articular α2-macroglobulin (A2M) has a chondroprotective effect in a collagen II-induced arthritis (CIA) mice model. Methods DBA/1 mice were randomized into four groups (n = 15/group): (a) CIA + 1.2 μg of A2M; (b) CIA + 0.8 μg of A2M; (c) CIA + 0.4 μg of A2M; (d) vehicle + phosphate-buffered saline (PBS). A2M was injected into right ankles and PBS was injected into the left ankles simultaneously as internal control at days 36, 43 and 50. The CIA inflammation clinical score and ankle thickness were recorded every other day starting on day 21 until sacrifice. Changes in inflammation were monitored by in vivo fluorescence molecular tomography (FMT). Inflammation, cartilage and bone damage were assessed with X-ray, histology and immunohistochemistry. Cartilage and inflammation-related gene expression was quantified by real-time polymerase chain reaction (PCR). Results All mice showed ankle inflammation on day 33. After day 43, lower clinical scores, ankle thickness and Sharp/van der Heijde method scores in A2M-treated ankles compared with PBS-treated ankles. FMT data indicated that the inflammation markers MMPSense and ProSense were significantly elevated in the PBS-treated ankles than A2M-treated ankles. Histology and X-ray analyses indicated that A2M administration resulted in lower levels of inflammatory infiltration and synovial hyperplasia, as well as more typical cartilage and bone organization with increased COL II and Aggrecan staining when compared with PBS-treated ankles. In addition, real-time PCR showed that,matrix metalloproteinase-3, -9, -13, COL X and Runx2 were significantly less expressed in A2M-treated groups than PBS-treated animals. Conclusion Early supplemental intra-articular A2M exerts an anti-inflammatory effect and attenuates cartilage and bone damage in a CIA model.
- Subjects :
- musculoskeletal diseases
Cartilage, Articular
Pathology
medicine.medical_specialty
Time Factors
medicine.medical_treatment
Anti-Inflammatory Agents
Arthritis
Inflammation
Article
Injections, Intra-Articular
03 medical and health sciences
0302 clinical medicine
Rheumatology
Foot Joints
Matrix Metalloproteinase 13
medicine
Animals
Aggrecans
030212 general & internal medicine
Collagen Type II
Saline
Aggrecan
030203 arthritis & rheumatology
business.industry
Foot Bones
Cartilage
Histology
medicine.disease
Arthritis, Experimental
Pregnancy-Associated alpha 2-Macroglobulins
Macroglobulin
medicine.anatomical_structure
Gene Expression Regulation
Mice, Inbred DBA
Cytokines
Female
Bone Remodeling
Inflammation Mediators
Ankle
medicine.symptom
business
Chondrogenesis
Subjects
Details
- ISSN :
- 1756185X and 17561841
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- International Journal of Rheumatic Diseases
- Accession number :
- edsair.doi.dedup.....928bc0de4f23e1f3788a6f76fe085b0e