Inflammation in osteoarthritis

Abstract

Purpose of review This review focuses on the novel stress-induced and proinflammatory mechanisms underlying the pathogenesis of osteoarthritis, with particular attention to the role of synovitis and the contributions of other joint tissues to cellular events that lead to the onset and progression of the disease and irreversible cartilage damage. Recent findings Studies during the past 2 years have uncovered novel pathways that, when activated, cause the normally quiescent articular chondrocytes to become activated and undergo a phenotypic shift, leading to the disruption of homeostasis and ultimately to the aberrant expression of proinflammatory and catabolic genes. Studies in animal models and retrieved human tissues indicate that proinflammatory factors may be produced by the chondrocytes themselves or by the synovium and other surrounding tissues, even in the absence of overt inflammation, and that multiple pathways converge on the upregulation of aggrecanases and collagenases, especially MMP-13. Particular attention has been paid to the contribution of synovitis in posttraumatic joint injury, such as meniscal tears, and the protective role of the pericellular matrix in mediating chondrocyte responses through receptors, such as discoidin domain receptor-2 and syndecan-4. New findings about intracellular signals, including the transcription factors NF-κB, C/EBPβ, ETS, Runx2, and hypoxia-inducible factor-2α, and their modulation by inflammatory cytokines, chemokines, adipokines, Toll-like receptor ligands, and receptor for advanced glycation end-products, as well as CpG methylation and microRNAs, are reviewed. Summary Further work on mediators and pathways that are common across different models and occur in human osteoarthritis and that impact the osteoarthritis disease process at different stages of initiation and progression will inform us about new directions for targeted therapies.

Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis

“…Moreover, increased production of pro-inflammatory and pro-catabolic mediators, like nitric oxide (NO), amplifies and perpetuates cartilage destruction (Boileau et al, 2002;Rosa et al, 2008;Sasaki et al, 1998). The transcription factor, Nuclear Factor-κB (NF-κB), and the family of mitogen-activated protein kinases (MAPK) play a central role in modulating the expression of those catabolic and inflammatory mediators (Goldring and Otero, 2011) and, thus, agents that suppress their activity have the potential to effectively decrease cartilage destruction and, therefore, OA progression (Berenbaum, 2004). Furthermore, compounds that can also restore anabolic and anti-catabolic gene expression have the potential to promote cartilage repair.…”

Does Intraarticular Inflammation Predict Biomechanical Cartilage Properties?

“…Obeid et al [35], however, showed that clinically, radiologically, and morphologically intact cartilage in the uninvolved compartment is mechanically inferior to cartilage from nonarthritic knees. Inflammation is recognized to play a substantial role in the pathogenesis of osteoarthritis [5,6,16,34]. In more recent years, several inflammatory mediators released by cartilage, bone, and synovium have been described [16,19,25].…”

“…Inflammation is recognized to play a substantial role in the pathogenesis of osteoarthritis [5,6,16,34]. In more recent years, several inflammatory mediators released by cartilage, bone, and synovium have been described [16,19,25]. Determination of the number of white blood cells (WBC) in the synovial fluid is a crucial diagnostic test in the discrimination between inflammatory or noninflammatory forms of joint effusion [14,43,47,49].…”

Update on biological therapies for knee injuries: osteoarthritis

“…During cartilage degradation, fragments of matrix components are released, such as aggrecan, collagen, and fibromodulin fragments, which maintain inflammatory cytokine production [7]. Furthermore, oxide synthase 2, cyclooxygenase (COX)-2, and prostaglandin E gene expression are increased as well, contributing to articular inflammation and destruction by enhancing the activation and production of MMPs and the inhibition of type II collagen proteoglycan synthesis [10].…”

“…Chondrocytes and synovial cells change their quiescent phenotype in response to an abnormal microenvironment from trauma-induced inflammation [7].…”