Molecular and cellular effects of intraarticular injection of betamethasone in experimental osteoarthritis

Kabalyk M.A., Nevzorova V.A., Dubov V.S., Tsygankov M.A., Kovalenko T.S.

Abstract


The objective of the study was to assess articular cartilage (AC) and subchondral bone (SCB) remodeling, expression of matrix metalloproteinase 9 (MMP-9) in tissues, vascular endothelial growth factor (VEGF) in experimental osteoarthritis (OA).
Material and methods
Experimental comparative study was conducted on 12 outbred guinea pigs of both sexes aged 28–30 weeks that were divided into 2 groups of 6 animals each. An injury to the knee joints of hind limbs of control and experimental animals was mechanically simulated by closed scarification using a sterile needle. No treatment was provided for controls. Experimental animals were given an intraarticular injection of betamethasone (BMZ) of 0.1 mg/kg every two weeks after two weeks of injury. Two subjects of each group were euthanized at 30, 45, 60 days and knee samples collected. Immunohistochemical expression of VEGF and MMP-9 was determined in tissues.
Results
A statistically significant decrease in VEGF positive chondrocytes and precipitate density, an increase in positive chondrocytes and intensity of tissue response to MMP-9 as compared to those in controls was observed in BMZ animals at 30 days of experiment. A statistically significant decrease in VEGF positive cells and precipitate density, an increase in VEGF positive chondrocytes as compared to those in controls were observed in BMZ animals at 45 days of experiment. Significant reduction in VEGF positive cells and deposit density, significantly higher density of MMP-9 positive precipitates as compared to those in controls were noted at 60 days of BMZ injections.
Conclusion
Intraarticular injections of BMZ demonstrated a negative effect on AC and SCB with articular tissue remodeling initiated through activation mechanisms of extracellular matrix degradation, as evidenced by high expression of MMP-9. BMZ was shown to block pathological angiogenesis via VEGF inhibition.

Keywords


osteoarthritis, vascular endothelial growth factor, matrix metalloproteinase 9, animal model, articular cartilage, subchondral bone

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DOI: http://dx.doi.org/10.18019/1028-4427-2020-26-1-65-71

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