Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway

Chem Biol Drug Des. 2020 Apr;95(4):451-459. doi: 10.1111/cbdd.13659. Epub 2020 Jan 14.

Abstract

This study investigated the mechanisms through which arctigenin promotes osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) from ovariectomized (OVX) rats were differentiated into osteoblasts, and osteogenesis was evaluated via Alizarin Red S (ARS) staining and alkaline phosphatase (ALP) measurements in cultured BMSCs. The levels of phosphorylated AKT serine/threonine kinase 1 (p-Akt), and peroxisome proliferator-activated receptor gamma (PPARγ) expression were quantified by Western blot analysis. The levels of urine calcium (U-Ca), urine phosphorus (U-P), serum ALP, and bone mineral density (BMD) of OVX rats were assessed in vivo. The results showed that treatment with arctigenin in rat BMSCs enhanced mineralization, increased ALP activity, increased the expression of Akt and p-Akt, and decreased PPARγ expression, consistent with its ability to promote osteoblast differentiation. Furthermore, arctigenin prevented OVX-induced osteoporosis in rats by increasing BMD and ALP activity and inhibiting the loss of Ca and P. In contrast, treatment with LY294002, a selective inhibitor of the phosphatidylinositol 3-kinase (PI3K), produced the opposite phenotype. These data suggest that the protective effects of arctigenin on BMSCs and OVX rat models result from the induction of osteogenesis involving the PI3K/Akt/PPARγ axis.

Keywords: BMSCs; PI3K; PPARγ; arctigenin; osteogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Calcium / urine
  • Cell Differentiation
  • Cell Proliferation
  • Furans / metabolism*
  • Gene Expression Regulation
  • Humans
  • Lignans / metabolism*
  • Mesenchymal Stem Cells / metabolism*
  • Osteoblasts / cytology
  • Osteogenesis
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorus / urine
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Signal Transduction

Substances

  • Furans
  • Lignans
  • PPAR gamma
  • Phosphorus
  • Proto-Oncogene Proteins c-akt
  • Alkaline Phosphatase
  • Calcium
  • arctigenin