A Synoviocyte Model for Osteoarthritis and Rheumatoid Arthritis: Response to Ibuprofen, Betamethasone, and Ginger Extract—A Cross-Sectional In Vitro Study

Abstract

This study aimed at determining if synovial cell cultures from rheumatoid arthritis (RA), osteoarthritis (OA), and healthy controls (HC) differ and are suitable disease models in pharmacological studies, and tested their response to some anti-inflammatory drugs. Synovial cells were isolated from synovial membrane or joint fluid. Cells were cultivated and exposed to no or TNF-α stimulation without, or in the presence of, betamethasone, ibuprofen, or a standardized ginger extract. Concentrations of a panel of cytokines, growth factors, and chemokines were mapped for each culture and condition. Our cells secreted an increased amount of the cytokines IL-1β, IL-6, and IL-8 in response to TNF-α stimulation in all conditions. OA cells showed a higher IL-6 and IL-8 and a lower IL-1β production, when not stimulated, than RA and HC cells, which were similar. TNF-α stimulation caused similar IL-1β, IL-6, and IL-8 release in all groups. Ibuprofen showed no effect on cytokine production, while ginger extract was similar to betamethasone. Ginger extract was as effective an anti-inflammatory agent as betamethasone in this in vitro model. Cultured fibroblast-like synoviocytes from OA and RA subjects promise to be a useful pharmacological disease model, but further studies, to support results from such a model are needed.

Toward understanding the role of cartilage particulates in synovial inflammation

“…The previously observed proliferative stimulus provided by these pro-inflammatory cytokines may have inhibited by the presence of growth factors in FBS used to supplement the culture media in the present study 42; 43 . Cytokine stimulated FLS have been shown to produce a number of inflammatory factors involved in OA and RA, including IL-6, IL-8, NO, and PGE2 23; 40; 41; 44 that can lead to matrix degradation, as observed here. PGE2 is known to activate MMP expression leading to cartilage degeneration 45 , reinforcing the role of the synovium in continued cartilage matrix degradation.…”

Role of Kletik oil, Ginger and Garlic Extracts towards Soft Tissue Injury

“…Additionally, another previous study stated that, ginger extract EV77/15 is as effective an anti-inflammatory agent as betamethasone in this in vitro cell model of cultured fibroblastlike synoviocytes. 10,11 In this study, it was found that ginger and its main components, gingerols, can inhibit synthesis of several pro-inflammatory cytokines including IL-1, TNF-α and IL-8 along with inhibiting prostaglandin (PG) and leukotriene (LT) synthesis enzymes. Furthermore, ginger also exerted effect on several genes encoding cytokines, chemokines and the inducible enzyme cyclo-oxygenase-2 (COX-2).…”

“…Due to their individual anti-inflammatory properties, when mixed together, these topical agents will have enhanced anti-inflammatory properties in treating soft tissue injuries. 3,4,9,10 Therefore, the objective of the study was to determine the effects of garlic, ginger and coconut oil (kletik oil) on soft tissue injury (swelling).…”

Medical Plant Extracts for Treating Knee Osteoarthritis: a Snapshot of Recent Clinical Trials and Their Biological Background

“…Similarly, extracts from two ginger species inhibited chemokine expression in primary OA synoviocytes [63]. A cross-sectional in vitro study of TNF-α-stimulated primary human synoviocytes showed that EV.EXT(R)77 ginger extract was an effective antiinflammatory agent comparable to betamethasone [64].…”