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.
Highlights
Development and introduction of effective, safe and pathogenetically substantiated therapies for osteoarthritis (OA) is regarded as a priority for the current orthopaedic practice
Non-operative treatments of OA outlined in Osteoarthritis Research Society International (OARSI) guidelines include nonpharmacological and pharmacological interventions employing non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, agents with structuremodifying effects, intra-articualr injections of hyaluronic acid and glucocorticosteroids [2]
There appears to be scant information related to the effects of corticosteriod therapy on the articular cartilage (AC) and subchondral bone (SCB) despite many-year experience of intra- and peri-articular injections used for OA
Summary
Development and introduction of effective, safe and pathogenetically substantiated therapies for osteoarthritis (OA) is regarded as a priority for the current orthopaedic practice. Non-operative treatments of OA outlined in Osteoarthritis Research Society International (OARSI) guidelines include nonpharmacological and pharmacological interventions employing non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, agents with structuremodifying effects, intra-articualr injections of hyaluronic acid and glucocorticosteroids [2]. It is suggested that local steroids can be applicable only in presence of synovitis of the OA joint [3]. Corticosteriod administration is associated with adverse effect on the biomechanical properties of articular tissues, the articular cartilage, in particular [4]. Systemic and local application of glucocorticosteroids has long been known to adversely affect bone quality and develop osteoporosis [5]. Recent studies report clinically relevant short-term benefits of corticosteriod therapy for pain and physical function in OA [2]. There appears to be scant information related to the effects of corticosteriod therapy on the AC and subchondral bone (SCB) despite many-year experience of intra- and peri-articular injections used for OA. There's concern that repeated cortisone injections might damage the cartilage within a joint
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