Amplification by (‑)‑epigallocatechin gallate of prostaglandin F2α‑stimulated synthesis of osteoprotegerin in osteoblasts

Mol Med Rep. 2017 Nov;16(5):6376-6381. doi: 10.3892/mmr.2017.7354. Epub 2017 Aug 24.

Abstract

(‑)‑Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), major flavonoids in green tea, and coffee, respectively, are recognized as possessing potential benefits in a multitude of human health conditions, including bone disorders. We have previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling mediator, stimulates the synthesis of osteoprotegerin (OPG) through the activation of p44/p42 mitogen‑activated protein kinase (MAPK), p38 MAPK and stress activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) in osteoblast‑like MC3T3‑E1 cells. In the present study, the effects of EGCG and CGA on PGF2α‑stimulated OPG synthesis in MC3T3‑E1 cells were investigated. EGCG significantly upregulated PGF2α‑stimulated OPG release, whereas CGA did not affect OPG release. The PGF2α‑induced expression level of OPG mRNA was enhanced by EGCG. Regarding the intracellular signaling underlying the effect of EGCG, EGCG failed to affect PGF2α‑stimulated phosphorylation of p44/p42 MAPK, p38 MAPK or SAPK/JNK. EGCG by itself markedly induced the phosphorylation of p44/p42 MAP kinase for up to 10 min and the status decreased subsequently, whereas EGCG did not significantly affect the phosphorylation status of p38 MAPK or SAPK/JNK within 60 min. These results indicated that EGCG, but not CGA amplifies the PGF2α‑stimulated OPG synthesis in osteoblasts.

MeSH terms

  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line
  • Chlorogenic Acid / pharmacology
  • Dinoprost / pharmacology*
  • Drug Synergism
  • Gene Expression Regulation
  • Mice
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoprotegerin / agonists
  • Osteoprotegerin / genetics*
  • Osteoprotegerin / metabolism
  • Phosphorylation / drug effects
  • RNA, Messenger / agonists
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Osteoprotegerin
  • RNA, Messenger
  • Tnfrsf11b protein, mouse
  • Chlorogenic Acid
  • Catechin
  • Dinoprost
  • epigallocatechin gallate
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 8
  • p38 Mitogen-Activated Protein Kinases