Abstract
Postmenopausal osteoporosis is a worldwide disease characterized by reduced bone mineral density and increased fracture risk. Inflammatory bone loss due to excessive osteoclast bone resorption is significant in the pathogenesis and development of osteoporosis. Punicalagin (PUN) is a pomegranate fruit derivative and has potential anti-inflammatory effects. However, the effect of PUN on osteoporotic bone loss has yet to be clarified. In this study, we investigated the effect of PUN on RANKL-induced osteoclast formation and bone resorption in vitro, as well as its potential therapeutic effect on ovariectomized-induced bone loss in vivo. PUN was demonstrated to suppress osteoclast formation and bone resorptive function dose-dependently, while osteoclast-specific genes were also downregulated by PUN. In vivo micro-CT and histopathological staining showed that the OVX procedure led to significant bone loss characterized by decreased bone parameters and increased osteoclast numbers, while PUN treatment dramatically prevented these changes. Furthermore, PUN treatment effectively inhibited proinflammatory cytokine expression in vitro. Mechanistically, PUN maintained bone mass via suppressing nuclear factor κB (NF-κB) and mitogen‐activated protein kinase (MAPK) signaling pathway activation. Collectively, our observations provide evidence that PUN is a potential candidate for the treatment of osteoporosis.
Highlights
Postmenopausal osteoporosis is a systemic metabolic bone disease that affects more than 200 million women worldwide (Zhao K. et al, 2019)
To determine the effect of PUN on osteoclast formation, RAW 264.7 macrophages were reseeded in 48-well plates and treated with 50 ng/ml RANKL in the presence or absence of various concentrations of PUN as indicated
Osteoclastogenesis inhibition by PUN was not due to cytotoxicity, as PUN (5–50 μM) did not affect cell viability. These results indicated that PUN possesses the ability to suppress osteoclast differentiation in the RANKL induction system without causing cytotoxic effects
Summary
Postmenopausal osteoporosis is a systemic metabolic bone disease that affects more than 200 million women worldwide (Zhao K. et al, 2019). It has been reported that one of three women older than 50 years will undergo osteoporotic fractures, which has a significant impact on the patients’ daily activities and quality of life, as well as significant economic costs for both individuals and society (Eriksen et al, 2014; Lin et al, 2016; An et al, 2019). Anti-osteoporotic drugs are efficacious, but they increase the potential risk of breast cancer, myocardial ischemia, thromboembolic disease, and atypical femur facture (Eriksen et al, 2014; Black and Rosen, 2016; Compston et al, 2019; Zhao K. et al, 2019). It is desirable to discover more efficacious and safer drugs for osteoporosis therapy
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