Shikimic acid prevents cartilage matrix destruction in human chondrocytes

Abstract

Abnormal reduction of extracellular matrix (ECM), including type II collagen and aggrecan, caused by tumor necrosis factor-α (TNF-α) is an important pathological feature of osteoarthritis (OA). Shikimic acid (SA), derived from natural plants, has displayed effective pharmacological properties in diverse diseases. The biological roles of SA in OA have not been reported before. Here, we found that treatment with SA (1 mM, 10 mM) prevented TNF-α-induced degradation of type II collagen and aggrecan ECM in human primary chondrocytes culture in vitro. Importantly, we also reported that SA treatment reduced TNF-α-induced expression of matrix metalloproteinase‑1, ‑3, and ‑13 (MMP‑1, ‑3, and ‑13) and increased expression of tissue inhibitor of metalloproteinase‑1 and ‑2 (TIMP‑1, ‑2). Additionally, SA treatment attenuated TNF-α-induced expression of a disintegrin and metalloprotease‑4 and ‑5 (ADAMTS‑4, ‑5). Mechanistically, we found that SA prevented activation of the nuclear factor-κB (NF‑κB) pathway. Our findings suggest that SA might act as an important therapeutic agent in the treatment of OA.

Keywords: Matrix metalloproteinases (MMP); Nuclear factor‑κB (NF‑κB); Osteoarthritis (OA); Shikimic acid (SA); Type II collagen.