Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway

Abstract

Purpose

Osteoarthritis (OA) is one of the most common degenerative joint diseases in the world, characterized primarily by the progressive degradation of articular cartilage. Accumulating evidence has shown that Morusin, a flavonoid derived from the root bark of Morus alba (mulberry) plants, exerts unique protective properties in several diseases. However, its effects on OA, specifically, have not yet been characterized.

Methods

In this study, we evaluated the anti-inflammatory effect of Morusin on mouse chondrocytes and its underlying mechanism in vitro. In addition, the protective effect of Morusin on destabilization of the medial meniscus (DMM) model was also explored in vivo.

Results

In vitro, IL-1β-induced activation of inflammatory factors (TNF-α, IL-6, INOS and COX2) was dramatically suppressed by Morusin. Further, Morusin treatment inhibited the expression of ADAMTS5 and metalloproteinase (MMPs), both of which regulate extracellular matrix degradation. Morusin also decreased IL-1β-induced p65 phosphorylation and IκBα degradation. In vivo, degradation of the articular cartilage following surgical DMM, which mimicked OA pathology, was abrogated following treatment with Morusin, thus demonstrating a protective effect in the DMM model.

Conclusion

Herein, we demonstrate that Morusin reduces the OA inflammatory response in vitro and protects against articular cartilage degradation in vivo potentially via regulation of the NF-κB pathway. Hence, Morusin may prove to be an effective candidate for novel OA therapeutic strategies.

Keywords:

• osteoarthritis
• chondrocytes
• Morusin
• IL-1β
• NF-κB pathway

Abbreviations

OA, osteoarthritis; IL-1β, interleukin-1β; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; INOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; MMP, matrix metalloproteinase; ADAMTS-5, A disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif; DMM, destabilization of the medial meniscus; MCE, MedChemExpress; ECM, extracellular matrix; NF-κB, nuclear factor kappa-B; BCA, bicinchoninic acid; CCK-8, cell counting kit-8; MAPK, mitogen-activated protein kinase; PI3K, The phosphatidylinositol 3ʹ -kinase.

Data Sharing Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Disclosure

Yewei Jia and Wei He are co-first authors for this study. The authors report no conflicts of interest in this work.