Abstract
The development and progression of osteoarthritis (OA) is associated with macrophage-mediated inflammation that generates a broad spectrum of cytokines and reactive oxygen species (ROS). This study investigates the effects of mid-MW hyaluronic acid (HA) in combination with a lactose-modified chitosan (CTL), on pro-inflammatory molecules and metalloproteinases (MMPs) expression, using an in vitro model of macrophage-mediated inflammation. Methods. To assess chondrocyte response to HA and CTL in the presence of macrophage derived inflammatory mediators, cells were exposed to the conditioned medium (CM) of U937 activated monocytes and changes in cell viability, pro-inflammatory mediators and MMPs expression or ROS generation were analysed. Results. CTL induced changes in chondrocyte viability that are reduced by the presence of HA. The CM of activated U937 monocytes (macrophages) significantly increased gene expression of pro-inflammatory molecules and MMPs and intracellular ROS generation in human chondrocyte cultures. HA, CTL and their combinations counteracted the oxidative damage and restored gene transcription for IL-1β, TNF-α, Gal-1, MMP-3 and MMP-13 to near baseline values. Conclusions. This study suggests that HA-CTL mixture attenuated macrophage-induced inflammation, inhibited MMPs expression and exhibited anti-oxidative effects. This evidence provides an initial step toward the development of an early stage OA therapeutic treatment
Highlights
Osteoarthritis (OA) is a progressive inflammatory degenerative disease that involves all the components of the joint- cartilage, bone, synovium, meniscus and infrapatellar fat pad and whose radiological signs can be found in more than 70% of people over 50 years of age [1,2]
The two major cytokines released by macrophages and implicated in early osteoarthritis (OA) are interlukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) that “awaken” chondrocytes from the metabolic state of rest and begin to synthesize, pro-inflammatory molecules and reactive oxygen species (ROS), that are added to those produced by inflammatory cells, and molecules and metalloproteinases (MMPs) [2]
To determine whether CTL alone or in combination with hyaluronic acid (HA) affected the viability of human chondrocytes, cells of three different donors were separately cultured in the presence or in the absence of different concentrations of the molecules
Summary
Osteoarthritis (OA) is a progressive inflammatory degenerative disease that involves all the components of the joint- cartilage, bone, synovium, meniscus and infrapatellar fat pad and whose radiological signs can be found in more than 70% of people over 50 years of age [1,2]. The extracellular matrix (ECM) molecules are mainly degraded by matrix metalloproteinases (MMPs) induced by inflammatory mediators [3]. Macrophage-mediated synovial inflammation is considered one of the main drivers of both OA development and progression [4]. An increased number of synovial macrophages in OA has been shown to be responsible for an increased expression of pro-inflammatory cytokines [5]. The two major cytokines released by macrophages and implicated in early osteoarthritis (OA) are interlukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) that “awaken” chondrocytes from the metabolic state of rest and begin to synthesize, pro-inflammatory molecules and reactive oxygen species (ROS), that are added to those produced by inflammatory cells, and MMPs [2]. Gal-1 acts as a regulator of inflammatory response in articular cells and tissues, either alone or in combination with Gal-3 and Galectin-8 [7,8]
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