Dietary phlorizin enhances osteoblastogenic bone formation through enhancing β-catenin activity via GSK-3β inhibition in a model of senile osteoporosis

• Published in: The Journal of nutritional biochemistry 2017-11, Vol.49, p.42-52
• Main Authors: Antika, Lucia Dwi, Lee, Eun-Jung, Kim, Yun-Ho, Kang, Min-Kyung, Park, Sin-Hye, Kim, Dong Yeon, Oh, Hyeongjoo, Choi, Yean-Jung, Kang, Young-Hee
• Format: Article
• Language: English
• Subjects: Animals; beta Catenin - agonists; beta Catenin - genetics; beta Catenin - metabolism; Biomarkers - metabolism; Bone and Bones - metabolism; Bone and Bones - pathology; Bone Density; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; Cell Line; Cell Survival; Chalcones - adverse effects; Chalcones - chemistry; Chalcones - therapeutic use; Dietary Supplements - adverse effects; Disease Models, Animal; Gene Expression Regulation, Developmental; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors; Glycogen Synthase Kinase 3 beta - genetics; Glycogen Synthase Kinase 3 beta - metabolism; Male; Mice; Osteoblastogenesis; Osteoblasts - metabolism; Osteoblasts - pathology; Osteogenesis; Osteoporosis - diet therapy; Osteoporosis - metabolism; Osteoporosis - pathology; Phloretin; Phloretin - adverse effects; Phloretin - therapeutic use; Phlorhizin - adverse effects; Phlorhizin - therapeutic use; Phlorizin; Senile osteoporosis; Specific Pathogen-Free Organisms; Wnt signaling; Wnt Signaling Pathway
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2017.07.014

Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss with advancing age has become a grave public health concern. This study examined whether phlorizin and phloretin, dihydrochalcones in apple peels, inhibited senile osteoporosis through enhancing osteoblastogenic bone formation in cell-based and aged mouse models. Submicromolar phloretin and phlorizin markedly stimulated osteoblast differentiation of MC3T3-E1 cells with increased transcription of Runx2 and osteocalcin. Senescence-accelerated resistant mouse strain prone-6 (SAMP6) mice were orally supplemented with 10 mg/kg phlorizin and phloretin daily for 12 weeks. Male senescence-accelerated resistant mouse strain R1 mice were employed as a nonosteoporotic age-matched control. Oral administration of ploretin and phorizin boosted bone mineralization in all the bones of femur, tibia and vertebra of SAMP6. In particular, phlorizin reduced serum RANKL/OPG ratio and diminished TRAP-positive osteoclasts in trabecular bones of SAMP6. Additionally, treating phlorizin to SAMP6 inhibited the osteoporotic resorption in distal femoral bones through up-regulating expression of BMP-2 and collagen-1 and decreasing production of matrix-degrading cathepsin K and MMP-9. Finally, phlorizin and phloretin antagonized GSK-3β induction and β-catenin phosphorylation in osteoblasts and aged mouse bones. Therefore, phlorizin and phloretin were potential therapeutic agents encumbering senile osteoporosis through promoting bone-forming osteoblastogenesis via modulation of GSK-3β/β-catenin-dependent signaling. [Display omitted]