Abstract
BackgroundThe purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and particularly on the expression of IL-10, TNF-alpha and beta1 integrin.MethodsHuman adult articular cartilage was obtained from 9 patients (6 male and 3 females), with primary knee osteoarthritis (OA), undergoing total joint replacement and from 3 young healthy donors (HD) (2 males, 1 female) with joint traumatic fracture. After isolation, chondrocytes underwent ESW treatment (electromagnetic generator system, MINILITH SL1, STORZ MEDICAL) at different parameters of impulses, energy levels and energy flux density. After that, chondrocytes were cultured in 24-well plate in DMEM supplemented with 10% FCS for 48 hours and then beta1 integrin surface expression and intracellular IL-10 and TNF-alpha levels were evaluated by flow-cytometry.ResultsAt baseline, osteoarthritic chondrocytes expressed significantly lower levels of beta1 integrin and higher levels and IL-10 and TNF-alpha levels. Following ESW application, while beta1 integrin expression remain unchanged, a significant decrease of IL-10 and TNF-alpha intracellular levels was observed both in osteoarthritic and healthy chondrocytes. IL-10 levels decreased at any impulses and energy levels, while a significant reduction of TNF-alpha was mainly found at middle energies.ConclusionOur study confirmed that osteoarthritic chondrocytes express low beta1 integrin and high TNF-alpha and IL-10 levels. Nonetheless, ESW treatment application down-regulate the intracellular levels of TNF-alpha and IL-10 by chondrocytes, suggesting that ESW might restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels. However, further in vivo and in vitro studies are necessary to establish if ESW can represent a viable option in the treatment of OA.
Highlights
The purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and on the expression of IL-10, TNF-alpha and beta1 integrin
In this study we provided evidence that ESW modulate intra-cellular levels of TNF-alpha and IL-10 by human articular chondrocytes both from osteoarthritic patients and healthy controls, without affecting beta1 integrin expression
ESW treatment seems to be capable to restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels potentially interfering with the pathologic mechanisms causing cartilage damage in OA and repre
Summary
The purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and on the expression of IL-10, TNF-alpha and beta integrin. Chondrocytes sense the changes of surrounding environment and this signalling between chondrocytes and ECM is crucial in maintaining cartilage homeostasis. These chondrocyte/ECM interactions are regulated by a large family of transmembrane glycoproteins whereby beta integrins are the most widely expressed and interact with several matrix proteins such as collagen, fibronectin, vitronectin and laminin [4]. In OA, beta integrin expression is significantly reduced in damaged cartilage [5] and this would alter chondrocyte/ECM interactions and disrupt beta integrin/GFr synergy leading to activation of catabolic pathways, increase of MMPs expression and induction of chondrocyte apoptosis
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