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.
Highlights
Matrix metalloproteinases (MMPs) are known to play an important role in the degradation of the extracellular matrix and the pathological progression of osteoarthritis (OA)
The loss of type II collagen and proteoglycans is due to the activation of extracellular matrix (ECM)degrading enzymes such as matrix metalloproteinases (MMPs) and ADAMTS [5]
Primary antibodies specific for Matrix metalloproteinase-13 (MMP-13), type II collagen, and actin were obtained from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA) and phosphorylated extracellular signal-regulated kinase (ERK) and phosphorylated p38 MAP kinase antibodies were purchased from Cell Signaling Technology Inc. (Danvers, MA, USA)
Summary
Matrix 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). Osteoarthritis (OA), the most common chronic and degenerative articular disease, is most prevalent in the elderly [1, 2]. The loss of type II collagen and proteoglycans is due to the activation of extracellular matrix (ECM)degrading enzymes such as matrix metalloproteinases (MMPs) and ADAMTS [5]. MMP-13 was reported to play important roles in the degradation of proteoglycans and the activation of pro-collagenase in the cartilage of individuals with OA [5, 6]
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