4.7 Article

Peonidin-3-O-glucoside and cyanidin increase osteoblast differentiation and reduce RANKL-induced bone resorption in transgenic medaka

Journal

PHYTOTHERAPY RESEARCH
Volume 35, Issue 11, Pages 6255-6269

Publisher

WILEY
DOI: 10.1002/ptr.7271

Keywords

apoptosis; cyanidin; osteoblasts; osteoclast; osteoporosis; p53; peonidin; RANKL; resveratrol; SIRT1

Funding

  1. National Center for Complementary and Integrative Health at the National Institutes of Health [R21 AT008452]
  2. University Grants Commission [5-66/2016(IC)]
  3. Schlumberger Foundation
  4. National Institutes of Health
  5. National Center for Complementary and Integrative Health

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Anthocyanins and resveratrol have been shown to promote proliferation and differentiation of human osteoblasts, reduce apoptosis, and regulate mitochondrial and epigenetic pathways, suggesting potential benefits for bone health.
Experimental and clinical studies suggest a positive impact of anthocyanins on bone health; however, the mechanisms of anthocyanins altering the differentiation and function of osteoblasts and osteoclasts are not fully understood. This work demonstrates that dietary anthocyanins and resveratrol increased proliferation of cultured human hFOB 1.19 osteoblasts. In addition, treatment of serum starvation of hFOB osteoblasts with anthocyanins and resveratrol at 1.0 mu g/ml reduced apoptosis, the Bax/Bcl-2 ratio, p53, and HDAC1 expression, but increased SIRT1/3 and PGC1 alpha mRNA expression, suggesting mitochondrial and epigenetic regulation. In Sp7/osterix:mCherry transgenic medaka, peonidin-3-O-glucoside and resveratrol increased osteoblast differentiation and increased the expression of Sp7/osterix. Cyanidin, peonidin-3-O-glucoside, and resveratrol also reduced RANKL-induced ectopic osteoclast formation and bone resorption in col10 alpha 1:nlGFP/rankl:HSE:CFP medaka in doses of 1-4 mu g/ml. The results indicate that both cyanidin and peonidin-3-O-glucoside have anabolic effects on bone, increasing osteoblast proliferation and differentiation, mitochondrial biogenesis, and by altering the osteoblast epigenome. Cyanidin and peonidin-3-O-glucoside also reduced RANKL-induced bone resorption in a transgenic medaka model of bone resorption. Thus, peonidin-3-O-glucoside and cyanidin appear to both increase bone formation and reduce bone loss, suggesting that they be further investigated as potential treatments for osteoporosis and osteomalacia.

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