Dishevelled‑2 modulates osteogenic differentiation of human synovial fibroblasts in osteoarthritis

Mol Med Rep. 2018 Jul;18(1):292-298. doi: 10.3892/mmr.2018.8975. Epub 2018 May 4.

Abstract

Dishevelled (Dvl)‑2 represents one of the cytoplasmic proteins, which serves as a pivotal hub in signaling intermediates through a number of different signaling pathways associated with the Wnt family. The aim of the present study was to investigate the roles and mechanisms of Dvl‑2 on synovial fibroblasts (SFBs) in osteoarthritis (OA). A Cell Counting kit‑8 (CCK‑8) assay was used to determine cell viability. An alkaline phosphatase (ALP) test kit was used to measure the activity of ALP. Western blot and reverse transcription‑quantitative polymerase chain reaction analysis were used to evaluate the protein and mRNA expression, respectively. The results suggest that depletion of Dvl‑2 significantly decreased the expression of osteoprotegerin (OPG) and ALP (P<0.05) and significantly increased the expression of receptor activator of nuclear factor‑κB ligand (RANKL), ALP, osteonectin (ON), osteocalcin (OCN) and osterix (P<0.05). In addition, the depletion of Dvl‑2 also significantly inhibited the expression of runt‑related transcription factor 2 (Runx‑2) and β‑catenin in SFBs (P<0.05). The effect of Dvl‑2 over‑expression was opposite to the effect of Dvl‑2 silencing. The inactivation of Wnt3a reversed the effect of Dvl‑2 silencing. In conclusion, the results indicate that Dvl‑2 regulated osteogenic differentiation of SFBs in OA.

MeSH terms

  • Aged
  • Alkaline Phosphatase / biosynthesis
  • Alkaline Phosphatase / genetics
  • Cell Differentiation*
  • Dishevelled Proteins / biosynthesis*
  • Dishevelled Proteins / genetics
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Osteogenesis*
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • Wnt3A Protein / genetics
  • Wnt3A Protein / metabolism

Substances

  • DVL2 protein, human
  • Dishevelled Proteins
  • WNT3A protein, human
  • Wnt3A Protein
  • Alkaline Phosphatase