Natural Compounds: Potential Therapeutics for the Inhibition of Cartilage Matrix Degradation in Osteoarthritis

Abstract

Osteoarthritis (OA) is the most common degenerative joint disease characterized by enzymatic degradation of the cartilage extracellular matrix (ECM) causing joint pain and disability. There is no disease-modifying drug available for the treatment of OA. An ideal drug is expected to stop cartilage ECM degradation and restore the degenerated ECM. The ECM primarily contains type II collagen and aggrecan but also has minor quantities of other collagen fibers and proteoglycans. In OA joints, the components of the cartilage ECM are degraded by matrix-degrading proteases and hydrolases which are produced by chondrocytes and synoviocytes. Matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS5) are the major collagenase and aggrecanase, respectively, which are highly expressed in OA cartilage and promote cartilage ECM degradation. Current studies using various in vitro and in vivo approaches show that natural compounds inhibit the expression and activity of MMP-13, ADAMTS4, and ADAMTS5 and increase the expression of ECM components. In this review, we have summarized recent advancements in OA research with a focus on natural compounds as potential therapeutics for the treatment of OA with emphasis on the prevention of cartilage ECM degradation and improvement of joint health.

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis

“…Subsequently, the levels of ECM-related proteins were determined. GPX7 overexpression promoted the accumulation of the ECM components, aggrecan and collagen II, and reduced the levels of MMP13 and ADAMTS5, which are key enzymes involved in cartilage degradation ( 24 ). The experimental results indicated that GPX7 has the ability to regulate and inhibit the aforementioned pathogenic factors.…”

Circulating levels of inflammatory cytokines and angiogenesis-related growth factors in patients with osteoarthritis after COVID-19

“…IL-1β and TNF-α, produced by immune cells, especially mononuclear cells, as well as activated chondrocytes, synoviocytes, and osteoblasts, are among the mediators that are released mainly in the early stages of OA ( 24 ). They are known to control the inflammatory cascade, induce the synthesis of matrix metalloproteinases (MMPs), nitric oxide, prostaglandin E2 (PGE2) and IL-6, reduce the synthesis of the main components of the extracellular matrix (ECM), while inhibiting the anabolic activity of chondrocytes and reduce the production of type II collagen ( 25 ). Catabolic events involving IL-1β and TNF-α are mediated through the activation of NF-κB intracellular signaling cascades.…”

Molecular mechanisms and potential applications of chondroitin sulphate in managing post-traumatic osteoarthritis

“…The canonical Wnt/β-catenin signalling is an another pathway up-regulated in joint trauma [ 45 ]. The maintenance of chondrocyte metabolic balance depends on baseline Wnt activity, while enhanced Wnt activity, as found in PTOA, can cause related extracellular matrix-degrading proteases to degrade cartilage matrix [ 46 ].…”