Trilobatin ameliorates bone loss via suppression of osteoclast cell differentiation and bone resorptive function in vitro and in vivo

Kim, Seong Cheol; Kim, Yang Soo; Park, Gi Eun; Pandey, Ramesh Prasad; Lee, Jisun; Sohng, Jae Kyung; Park, Yong Il

doi:10.1016/j.lfs.2021.119074

Cited by 5 publications

(1 citation statement)

References 26 publications

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“…Recently, it has been described that adipocytes in bone marrow can affect bone resorption, through the expression of RANKL and OPG [22,84]. Furthermore, the treatment of ovariectomized mice with phloretin protected them from bone-mass loss and increased OPG/RANKL ratio in serum [85,86]. In relation to these studies, our preliminary results suggest that the inhibitory effect of phloretin on bone resorption may be mediated, in part, by its ability to increase OPG expression and OPG/RANKL ratio in bone marrow adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

et al. 2021

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Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG/RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide.

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