Rosmarinic acid induces rabbit articular chondrocyte differentiation by decreases matrix metalloproteinase-13 and inflammation by upregulating cyclooxygenase-2 expression

Abstract

BackgroundMatrix metalloproteinases (MMPs) are known to play an important role in the degradation of the extracellular matrix and the pathological progression of osteoarthritis (OA). The natural polyphenolic compound rosmarinic acid (Ros. A) has been shown to suppress the inhibitory activity of matrix metalloproteinases (MMPs). However, the effects of Ros. A on OA have not been investigated.MethodsIn the current study, primary articular chondrocytes were cultured from rabbit articular cartilage and treated with Ros. A. Phenotypic characterization was performed by western blotting to assess specific markers, prostaglandin E2 (PGE2) assays, and alcian blue staining to measure sulfated-proteoglycan production.ResultsWe report that in rabbit articular chondrocytes, Ros. A increased type II collagen, sulfated-proteoglycan, cyclooxygenase-2 (COX-2), and PGE2 production in a dose- and time-dependent manner. Furthermore, Ros. A suppressed the expression of MMP-13. In addition, treatment with Ros A activated extracellular signal-regulated kinase (ERK)-1/2 and p38 kinase signaling pathways. Inhibition of MMP-13 enhanced Ros. A-induced type II collagen expression and sulfated-proteoglycan synthesis but COX-2 and PGE2 production were unchanged. Ros. A-mediated up-regulation of ERK phosphorylation was abolished by the MEK inhibitor, PD98059, which prevented induction of the associated inflammatory response. Inhibition of p38 kinase with SB203580 enhanced the increase in type II collagen expression via Ros. A-mediated down-regulation of MMP-13.ConclusionsResults suggest that ERK-1/2 regulates Ros. A-induced inflammation and that p38 regulates differentiation by inhibiting MMP-13 in rabbit articular chondrocytes.

The inhibitory effects of rosmarinic acid on catabolism induced by IL-1β in rat chondrocyte

“…Our results showed that RosA can inhibit the secretion of IL-6.Therefore, the protective effects of RosA on chondrocytes may be partly associated with its antiinflammatory properties. However, Eo and others (Eo et al, 2017) reported that RosA can induce COX-2, another inflammatory cytokine, in rabbit chondrocytes. Thus, the role of RosA in OA is still unclear.…”

Effect of Dietary Polyphenols on Osteoarthritis—Molecular Mechanisms

“…In rabbit articular chondrocytes, rosmarinic acid treatment increased differentiation of chondrocytes coupled with increased production of COL-II, sulfated-proteoglycan, COX-2, and PGE2. In addition, rosmarinic activated the ERK-1/2 and p38 kinase signaling pathways [ 80 ]. In another study on IL-1β-induced rat chondrocytes, rosmarinic acid inhibited the production of IL-6, downregulated gene and protein expression of ADAMTS-4 and ADAMTS-5, and abolished the IL-1β-induced inhibition of ACAN and COL2 gene expression [ 81 ].…”

Antioxidant Activity and Anti-Photoaging Effects on UVA-Irradiated Human Fibroblasts of Rosmarinic Acid Enriched Extract Prepared from Thunbergia laurifolia Leaves

“…The previous research indicated that Rosmarinus officinalis L. extract containing rosmarinic acid, carnosol, and carnosic acid had been shown to protect against UV-induced MMP-1 in human dermal fibroblasts and reconstructed skin [ 31 ]. Rosmarinic acid was also shown to inhibit MMP-2 and MMP-13 activity [ 32 , 33 , 34 ] and was recently reported to protect human fibroblasts from damage and stimulates collagen biosynthesis [ 35 ]. Our results indicated a potential candidate of SRAEE prepared from dechlorophyll of T. laurifolia leaf, which exhibited antioxidant activity and anti-photoaging effects on UVA-irradiated NHDF cells as a natural active pharmaceutical ingredient for cosmeceutical product application.…”