Emodin protects knee joint cartilage in rats through anti-matrix degradation pathway: An in vitro and in vivo study

Life Sci. 2021 Mar 15:269:119001. doi: 10.1016/j.lfs.2020.119001. Epub 2021 Jan 6.

Abstract

Aims: Osteoarthritis (OA) is a common joint disease and the main cause of disability. We sought to determine the effective concentration of emodin on chondrocytes and to identify the dosage of emodin that induces a comparable therapeutic effect with the COX-2 inhibitor drug, celecoxib that is currently used to treat OA.

Material and methods: In vitro experiments induced inflammation of chondrocytes by IL-1β, and an osteoarthritis model was established in vivo by cutting rat anterior cruciate ligament. Western Blot, Real-time PCR, HE staining, Safranin O-green staining and immunohistochemistry were performed to detect MMP-3, MMP-13, ADAMTS-4, iNOS and COL2A1 on the chondrocytes or the tibial plateau. The cytokine activity and content in serum of six groups of rats were measured by kit.

Results: It was found that the surface layer of the cartilage was thicker and smoother after the administration of emodin. Tissue expression of MMP-3, MMP-13, ADAMTS-4 and iNOS were significantly (p < 0.05) decreased in chondrocytes and cartilage treated with different doses of emodin, and the content of COL2A1 was reversed. Emodin also significantly decreased the blood levels of COX-2 and PGE2. The effective emodin in vitro was 5 μmol/L, whereas emodin at 80 mg/kg was equivalent to celecoxib in vivo.

Conclusion: Emodin reduces the expression of cartilage matrix degradation biomarkers, thereby reducing the degradation of cartilage matrix and protecting the knee joint cartilage. Emodin at 5 μmol/L shows the best concentration to treat chondrocytes, and the protective effect of emodin at 80 mg/kg is comparable to that of celecoxib.

Keywords: Cartilage; Emodin; Osteoarthritis; Rats; Therapeutic.

MeSH terms

  • ADAMTS4 Protein / metabolism
  • Animals
  • Cartilage, Articular / pathology*
  • Cell Survival / drug effects
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Cyclooxygenase 2 / blood
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Emodin / administration & dosage
  • Emodin / pharmacology*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Gene Expression Regulation / drug effects
  • Knee Joint / pathology*
  • Matrix Metalloproteinases / metabolism
  • Nitric Oxide / blood
  • Nitric Oxide Synthase Type II / blood
  • Nitric Oxide Synthase Type II / metabolism
  • Protective Agents / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / pathology

Substances

  • Protective Agents
  • RNA, Messenger
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Matrix Metalloproteinases
  • ADAMTS4 Protein
  • Dinoprostone
  • Emodin