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

Abstract

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 μg/ml reduced apoptosis, the Bax/Bcl-2 ratio, p53, and HDAC1 expression, but increased SIRT1/3 and PGC1α mRNA expression, suggesting mitochondrial and epigenetic regulation. In Sp7/osterix:mCherry transgenic medaka, peonidin-3-Oglucoside and resveratrol increased osteoblast differentiation and increased the expression of Sp7/osterix. Cyanidin, peonidin-3-O-glucoside, and resveratrol also reduced RANKLinduced ectopic osteoclast formation and bone resorption in col10α1:nlGFP/rankl:HSE:CFP medaka in doses of 1-4 μg/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.

A Comparison of the Antiosteoporotic Effects of Cornelian Cherry (Cornus mas L.) Extracts from Red and Yellow Fruits Containing Different Constituents of Polyphenols and Iridoids in Osteoblasts and Osteoclasts

“…It has been proven that bone metabolism can be modulated by nutrients [ 2 , 3 ]. Recently published studies have reported that polyphenols, especially anthocyanins [ 4 , 5 ], phenolic acids [ 6 ], and flavonols [ 7 ], as well as iridoids [ 8 ] and hydrolysable tannins [ 9 ] can prevent bone loss through different mechanisms. All these substances are present in cornelian cherries, in varying amounts, making their extracts promising candidates for antiosteoporotic agents.…”

Polyphenolic profiles of a variety of wild berries from the Pacific Northwest region of North America

“…This suggests that the anthocyanins profile of the huckleberries accessions 9JOA3679-2, 9JOA3678-1, and 9JOA3682-3 may be particularly beneficial in terms of potential nutrition and health outcomes. Peonidins have received less attention for health research ( Ren et al, 2021 ; Semmarath et al, 2022 ), but peonidins levels are only slightly higher than in blueberries, so the two other accessions are mostly different in terms of their cyanidins and malvidins levels.…”

Anthocyanins in Chronic Diseases: The Power of Purple

“…Davidson’s plum containing cyanidin 3-glucoside (8 mg/kg/day) reduced obesity-induced degeneration of knee cartilage in rats with diet-induced metabolic syndrome [ 67 ]. In osteoporosis, bone regeneration may be stimulated by anthocyanins by stimulating bone formation and inhibiting bone resorption [ 245 ]; examples include peonidin 3-glucoside and cyanidin [ 246 ]. Anthocyanins may also alter bone remodelling in osteoporosis by epigenetic regulation of osteoblast differentiation and apoptosis, and bone mineralisation [ 247 ].…”

“…The hypothesis of a “gut–joint axis” has been proposed to connect the changes in the gut microbiota and osteoarthritis factors such as age, gender, metabolism, central nervous system and joint injury [ 246 , 248 ]. Decreasing serum lipopolysaccharides and inflammatory responses by chronic ampicillin and neomycin treatment of osteoarthritic mice changed the microbiota and improved the signs of osteoarthritis [ 249 ].…”