Resveratrol protects MC3T3-E1 cells against cadmium-induced suppression of osteogenic differentiation by modulating the ERK1/2 and JNK pathways

Ecotoxicol Environ Saf. 2021 May;214:112080. doi: 10.1016/j.ecoenv.2021.112080. Epub 2021 Mar 5.


Resveratrol (RES) is a natural polyphenolic compound with a broad range of physiological and pharmacological properties. Previous studies have shown that RES also plays an important role in protecting and promoting early bone metabolism and differentiation. The accumulation of cadmium (Cd), one of the world's most poisonous substances, can inhibit skeletal growth and bone maturation, thus causing osteoporosis. However, whether RES can prevent the Cd-induced inhibition of osteogenic differentiation remains unknown. In this study, we found that RES promoted the early maturity of osteoblastic MC3T3-E1 cells, as demonstrated by the significantly increased mRNA and protein expression of a range of differentiation markers, including alkaline phosphatase (ALP), collagen 1 (COL1), bone morphogenetic protein-2 (BMP-2), and runt-related transcription factor 2 (RUNX2). In contrast, we found that cadmium chloride (CdCl2) inhibited the viability and osteogenic maturity of MC3T3-E1 cells. We also demonstrated that RES pretreatment for 30 min provided significant protection against Cd-induced apoptosis and attenuated the inhibition of osteogenic differentiation induced by Cd by modulating ERK1/2 and JNK signaling. In conclusion, our results indicate that RES is a potential femoral protectant that not only enhance the viability and early differentiation of osteoblasts, but also protect osteoblasts from cadmium damage.

Keywords: Cadmium; Mitogen-activated protein kinases; Osteoblast; Osteogenic differentiation; Resveratrol.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2
  • Cadmium / metabolism
  • Cadmium / toxicity*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Core Binding Factor Alpha 1 Subunit
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase 3
  • Osteoblasts / cytology
  • Osteogenesis / genetics
  • Protective Agents / pharmacology*
  • Resveratrol / pharmacology*


  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • Protective Agents
  • RUNX2 protein, human
  • Cadmium
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 3
  • Alkaline Phosphatase
  • Resveratrol