Effect of Tart Cherry Polyphenols on Osteoclast Differentiation and Activity

J Med Food. 2020 Jan;23(1):56-64. doi: 10.1089/jmf.2019.0050. Epub 2019 Aug 22.


Bone is maintained by an intricate balance between bone formation and bone resorption. The presence of inflammation can contribute to an imbalance in bone homeostasis by enhancing differentiation and activity of osteoclasts, the cells that participate in the breakdown of bone. Polyphenols such as flavonoids found in plant-derived foods have been shown to have anti-inflammatory effects in various tissues. Tart cherries are a rich source of such polyphenolic compounds. Using mouse macrophage cells (RAW 264.7), we examined whether tart cherry polyphenols could dose dependently inhibit the proliferation and activity of receptor activator of nuclear factor kappa-B ligand (RANKL) differentiated osteoclasts under inflammatory conditions. Tartrate-resistant acid phosphatase (TRAP) activity and staining of TRAP-positive multinucleated cells, used as indicators of osteoclast differentiation and activity, tended to decrease with tart cherry polyphenols treatment. Osteoprotegerin expression by osteoclasts was decreased in a similar manner. A significant increase in nitrite concentration was observed with the lower doses of tart cherry polyphenols of 50 and 100 μg/mL (P < .05). However, higher doses of tart cherry polyphenols (200 and 300 μg/mL) reduced nitrite concentrations below that of the control that received no tart cherry polyphenols treatment (P < .05). Western blot analyses showed that protein expression of cyclooxygenase-2 (COX-2) followed a similar trend, although results were not statistically significant. On the other hand, tart cherry polyphenols treatments dose dependently increased inducible nitric oxide synthase protein expression, with statistical significance noted at doses of 200 and 300 μg/mL. Overall, our findings suggest that the polyphenols associated with tart cherries potentially inhibit osteoclast differentiation and activity, which may be beneficial to bone health.

Keywords: inflammation; macrophages; osteoclastogenesis; osteoclasts; polyphenols; tart cherry.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cyclooxygenase 2 / metabolism
  • Fruit / chemistry*
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Nitrites / analysis
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Osteoprotegerin / metabolism
  • Plant Extracts / pharmacology
  • Polyphenols / pharmacology*
  • Prunus avium / chemistry*
  • RANK Ligand / metabolism
  • RAW 264.7 Cells
  • Tartrate-Resistant Acid Phosphatase / metabolism


  • Nitrites
  • Osteoprotegerin
  • Plant Extracts
  • Polyphenols
  • RANK Ligand
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Tartrate-Resistant Acid Phosphatase