Dried Plum Polyphenols Inhibit Osteoclastogenesis by Downregulating NFATc1 and Inflammatory Mediators

Abstract

Dried plums and their polyphenols have been shown to suppress bone resorption by downregulating receptor activator NF-kappaB ligand (RANKL). Due to the anti-inflammatory and antioxidant properties of these compounds, this study was designed to investigate whether dried plum polyphenols exert additional, more direct effects on osteoclasts and their precursors. RAW 264.7 macrophages were used as a model to study osteoclast precursors and osteoclast differentiation and activity. Under inflammatory conditions induced by lipopolysaccharide (LPS), polyphenols extracted from dried plum (10, 20, and 30 microg/mL) downregulated osteoclast precursor cyclooxygenase expression and nitric oxide (NO) by inhibiting inducible NO synthase. NO and tumor necrosis factor (TNF)-alpha were also suppressed in the presence of RANKL during osteoclastogenesis by the polyphenols. Increased TNF-alpha production in response to oxidative stress, but not LPS, was decreased over time. As expected, LPS and H2O2 significantly increased the number of tartrate-resistant acid phosphatase-positive cells by 127% and 30%, respectively. Dried plum polyphenols decreased osteoclast differentiation under normal as well as inflammatory and oxidative stress conditions, coincident with the suppression of the transcription factor, nuclear factor for activated T cells (NFATcl). These inhibitory effects on osteoclastogenesis were confirmed in primary bone marrow cultures. Resorption pit formation was decreased to a similar extent as osteoclast differentiation, suggesting that dried plum polyphenols primarily affect osteoclast differentiation as opposed to activity. Our data demonstrate that dried plum polyphenols directly inhibit osteoclastogenesis, leading to a decrease in osteoclast activity, by downregulating NFATc1 and inflammatory mediators.

A Systematic Review on the Health Effects of Plums (Prunus domestica and Prunus salicina)

“…The results from this in vitro experiment by Bu et al (2008) has also been confirmed in animal studies (Deyhim et al, 2005;Franklin et al, 2006;Bu et al, 2007;Smith et al, 2014a). Among these, the study by Smith et al (2014a) is slightly different in that unlike the other studies that studied longer term effects of dried plum on systemic biochemical markers of bone metabolism and alteration in gene expression as the main outcome measure, their main objective was to understand the mechanism of action by which dried plum altered bone metabolism.…”

Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases

“…Part of the rescued bone phenotype was attributed to antioxidant effects on the osteoblast since ROS, which increases in animal models after operations to induce sex hormone deficiency, has been shown to upregulate expression of RANKL [60]. Additional studies revealed that dried plum polyphenols also cause decreased osteoclast differentiation, NFATc1 expression, and bone resorption [61]. Simvastatin, a 3-hydroxy-3 methylglutaryl coenzyme A (HMG Co-A) reductase inhibitor, used to treat high cholesterol, has also been shown to function as an antioxidant that can affect bone formation and resorption.…”

Melittophilous Mode of Pollination Predominates in European Plum (Prunus domestica L.) in the Semi-Arid Environment of Northwest India

“…Prunes improve the liver function (Ahmed et al, 2010b), bone health (Hooshmand and Arjmandi, 2009. ) and increase bone mass, prevents osteoporosis (Deyhim et al, 2005;Bu et al, 2008), enhances the resistance to fungal infection (El-Kereamy et al, 2011), is anticancerous (Fujii et al, 2006) and anti hypercholestremia (Tinker et al, 1991).…”