Scutellarin ameliorates cartilage degeneration in osteoarthritis by inhibiting the Wnt/β-catenin and MAPK signaling pathways

Int Immunopharmacol. 2020 Jan:78:105954. doi: 10.1016/j.intimp.2019.105954. Epub 2019 Nov 19.

Abstract

Osteoarthritis (OA) is a chronic inflammatory disease that is the basis of cartilage extracellular matrix degeneration and joint inflammation. Scutellarin is an herbal flavonoid glucuronide, isolated from the Chinese traditional herb Erigeron breviscapus, has been reported to have anti-inflammatory effect. Here, we showed that Scutellarin could inhibit inflammation and protects cartilage from degeneration in vitro and in vivo. Scutellarin downregulate the mRNA and protein expression of MMP1, MMP13, and ADAMTS-5, Wnt3a, Frizzled7 and promote the expression of Collagen II and Aggrecan. Moreover, scutellarin inhibit the migration of β-catenin and phosphorylation of p38 into the nucleus, which may relate to the mediation of the Wnt/β-catenin and MAPK signaling pathway. Furthermore, scutellarin significantly inhibit the cartilage degradation of DMM-induced OA mice by safranin-O and fast green staining. In conclusion, our study indicates that scutellarin may be a potential drug for the treatment of OA.

Keywords: Aggrecan; Collagen II; MMPs; Osteoarthritis; Scutellarin; β-Catenin.

MeSH terms

  • ADAMTS5 Protein / genetics
  • ADAMTS5 Protein / metabolism
  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apigenin / pharmacology
  • Apigenin / therapeutic use*
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Glucuronates / pharmacology
  • Glucuronates / therapeutic use*
  • Humans
  • Knee Joint / drug effects
  • Knee Joint / pathology
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Mice, Inbred C57BL
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Wnt Signaling Pathway / drug effects*
  • Wnt3A Protein / genetics
  • Wnt3A Protein / metabolism

Substances

  • Aggrecans
  • Anti-Inflammatory Agents
  • Collagen Type II
  • FZD7 protein, human
  • Frizzled Receptors
  • Glucuronates
  • Wnt3A Protein
  • scutellarin
  • Apigenin
  • ADAMTS5 Protein
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 1