Fisetin promotes osteoblast differentiation and osteogenesis through GSK-3β phosphorylation at Ser9 and consequent β-catenin activation, inhibiting osteoporosis

Molagoda, Ilandarage Menu Neelaka; Kang, Chang‐Hee; Lee, Mi-Hwa; Choi, Yung Hyun; Lee, Chang-Min; Lee, Seungheon; Kim, Gi‐Young

doi:10.1016/j.bcp.2021.114676

Cited by 32 publications

(29 citation statements)

References 38 publications

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“…Fisetin, a naturally occurring flavonoid with less toxicity than navitoclax [ 87 ] also proved to protect bone. Repression of osteoclasts [ 81 ] and promotion of osteoblast differentiation [ 82 ] seem to be the pathways responsible for the positive effects on BTMs, BMD, and bone microarchitecture.…”

Section: Treatment Options To Target Osteoporosis and Senescencementioning

confidence: 99%

Age Related Osteoporosis: Targeting Cellular Senescence

Föger-Samwald

Kerschan‐Schindl

Butylina

et al. 2022

IJMS

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Age-related chronic diseases are an enormous burden to modern societies worldwide. Among these, osteoporosis, a condition that predisposes individuals to an increased risk of fractures, substantially contributes to increased mortality and health-care costs in elderly. It is now well accepted that advanced chronical age is one of the main risk factors for chronical diseases. Hence, targeting fundamental aging mechanisms such as senescence has become a promising option in the treatment of these diseases. Moreover, for osteoporosis, the main pathophysiological concepts arise from menopause causing estrogen deficiency, and from aging. Here, we focus on recent advances in the understanding of senescence-related mechanisms contributing to age-related bone loss. Furthermore, treatment options for senile osteoporosis targeting senescent cells are reviewed.

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Section: Treatment Options To Target Osteoporosis and Senescencementioning

confidence: 99%

Age Related Osteoporosis: Targeting Cellular Senescence

Föger-Samwald

Kerschan‐Schindl

Butylina

et al. 2022

IJMS

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“…In addition, the downregulation of RUNX2 and OSX transcriptional activities has been found in PDS-treated mice concomitant with decreased bone area and thickness [ 16 ], confirming that PDS has a negative impact on osteoblast differentiation. In our previous study [ 31 ], direct action of PDS was also found to downregulate the gene expression of OCN , ALP , and Col1α1 in both mouse preosteoblast MC3T3-E1 and zebrafish larvae, impairing the synthesis of extracellular matrix components. Furthermore, PDS remarkably stimulates the expression of matrix metalloproteases (MMPs), including MMP-2, MMP-9, and MMP-13 in mice [ 32 ], which subsequently degrades all types of extracellular matrix (ECM) proteins, suggesting that the anti-osteoblast activities of PDS may also be linked to the degradation of ECM components.…”

Section: Discussionmentioning

confidence: 96%

“…Furthermore, PDS remarkably stimulates the expression of matrix metalloproteases (MMPs), including MMP-2, MMP-9, and MMP-13 in mice [ 32 ], which subsequently degrades all types of extracellular matrix (ECM) proteins, suggesting that the anti-osteoblast activities of PDS may also be linked to the degradation of ECM components. Furthermore, osteoclastogenesis was previously identified in response to PDS treatment in both zebrafish and mouse models, accompanied by specific expression of osteoclast-specific genes [ 16 , 30 , 31 ]. Interestingly, we found that FO, under both PDS-pretreated and post-treated conditions, cured and prevented PDS-mediated bone mineralization and resorption in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, E2 induced ERE-luciferase activity in estrogen-responsive MCF-7 breast cancer cells and increased proliferation, but not in FO-treated MCF-7 cells. Previously, we also reported that FO did not directly bind to estrogen receptors and androgen receptors and did not show any changes in the weight of the androgen- and estrogen-dependent organs [ 31 ]. Overall, these results indicate that FO promotes osteoblast differentiation and vertebral formation regardless endocrine disturbance.…”

Section: Discussionmentioning

confidence: 99%

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Fermented Oyster (Crassostrea gigas) Extract Cures and Prevents Prednisolone-Induced Bone Resorption by Activating Osteoblast Differentiation

Molagoda

Athapaththu

Park

et al. 2022

Foods

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Osteoporosis is a bone resorptive disease characterized by the loss of bone density, causing an increase in bone fragility. In our previous study, we demonstrated that gamma aminobutyric acid-enriched fermented oyster (Crassostrea gigas) extract (FO) stimulated osteogenesis in MC3T3-E1 preosteoblast cells and vertebral formation in zebrafish. However, the efficacy of FO in prednisolone (PDS)-induced bone resorption remains unclear. In this study, we evaluated the osteogenic potential of FO in MC3T3-E1 preosteoblast cells and zebrafish larvae under both PDS-pretreated and PDS-post-treated conditions. We found that FO recovered osteogenic activity by upregulating osteoblast markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2, and osterix, in both PDS-pretreated and post-treated MC3T3-E1 osteoblast cells and zebrafish larvae. In both conditions, PDS-induced decrease in calcification and ALP activity was recovered in the presence of FO. Furthermore, vertebral resorption in zebrafish larvae induced by pretreatment and post-treatment with PDS was restored by treatment with FO, along with the recovery of osteogenic markers and downregulation of osteoclastogenic markers. Finally, whether FO disturbs the endocrine system was confirmed according to the Organization for Economic Cooperation and Development guideline 455. We found that FO did not stimulate estrogen response element-luciferase activity or proliferation in MCF7 cells. Additionally, in ovariectomized mice, no change in uterine weight was observed during FO feeding. These results indicate that FO effectively prevents and treats PDS-induced osteoporosis without endocrine disturbances.

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“…demonstrated that Fisetin could accelerate the osteoblast differentiation through activating the phosphorylation of GSK-3β at Ser9, thereby ameliorating osteoporosis. 22 Chen et al. reported a positive association between Scara3 and osteogenic differentiation of BM-MSCs.…”

Section: Discussionmentioning

confidence: 99%