Eldecalcitol prevented OVX-induced osteoporosis through inhibiting BMSCs senescence by regulating the SIRT1-Nrf2 signal

Kou, Yuying; Rong, Xing; Tang, Rong; Zhang, Yuan; Yang, Panpan; Liu, Hongrui; Ma, Wenqi; Li, Minqi

doi:10.3389/fphar.2023.1067085

Cited by 12 publications

(5 citation statements)

References 59 publications

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“… 31 In order to explore the effect of ED-71 on osteoclasts, we established the postmenopausal osteoporosis model in rats based on our previous report. 26 Our results showed that the tibial bone mass and the new bone formation was reduced, indicating the successful establishment of the model. The postmenopausal osteoporosis is found to be in a state of oxidative stress.…”

Section: Discussionmentioning

confidence: 50%

“… 32 We used H 2 O 2 stimulated MC3T3-E1 cells as in vitro model, simulating those growing in osteoporosis environment. 26 The results showed that H 2 O 2 increased osteoclast generation, as well as the protein and mRNA expression of CtsK and MMP9, both are related to the ability of osteoclast to undergo bone resorption.…”

Section: Discussionmentioning

confidence: 92%

“…Culturing dishes or flasks were placed in a 37°C, 5% CO 2 incubator. According to our previous study, 26 the cells were stimulated with H 2 O 2 to imitate the cell environment of osteoporosis in vitro. MC3T3-E1 cells were pre-stimulated with 100 μM H 2 O 2 for 2 hours.…”

Section: Methodsmentioning

confidence: 99%

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ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis

Wang,

Kou,

Rong

et al. 2024

DDDT

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Purpose Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71. Methods In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, H 2 O 2 stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot. Results ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts. Conclusion ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 92%

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ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis

Wang,

Kou,

Rong

et al. 2024

DDDT

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“…showed that melatonin promotes the osteogenic potential of BMSCs by regulating SIRT1-mediated antioxidant properties [29]. Eldecalcitol inhibits BMSC senescence by modulating the SIRT1-Nrf2 pathway [60]. Based on these findings, we further investigate whether carvacrol regulates SIRT1 to influence the osteogenic differentiation of BMSCs.…”

Section: Discussionmentioning

confidence: 83%

Carvacrol induces osteogenic differentiation of BMSCs and alleviates osteolysis in aged mice by upregulating lncRNA NEAT1 to promote SIRT1 expression

Xu,

Wang,

et al. 2023

APT

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Background: Wear particle-induced periprosthetic osteolysis is a major contributor to joint replacement failure and revision surgery in the elderly. Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is a promising approach for bone regeneration. Carvacrol may have bone-protective potential. This study investigated whether carvacrol alleviates osteolysis and promotes osteogenic differentiation of BM-SCs by regulating SIRT1 expression. Materials and Methods: An osteolysis model in aged mice was established by titanium (Ti) particle induction. BMSCs were isolated from femur and tibia of 18-month-old mice and cultured in osteogenic differentiation medium. RIP and RNA pull-down were used to evaluate the binding of SIRT1 and lncRNA NEAT1. Ubiquitination analysis was performed to investigate NEAT1-mediated regulation of SIRT1 ubiquitination modification levels. Results: Carvacrol treatment improved Ti particle-induced calvarial erosion and attenuated osteolysis. Carvacrol increased SIRT1 both in the mouse model of Ti-induced osteolysis and in BMSCs under osteogenic differentiation. Carvacrol treatment promoted ALP activity, bone mineralization capacity, and expression of osteogenic differentiation-related factors, whereas SIRT1 knockdown reversed this effect. LncRNA NEAT1 interacted with SIRT1, and overexpression of NEAT1 stabilized SIRT1 by inhibiting its ubiquitination modification. NEAT1 knockdown altered the promoting effect of carvacrol on osteogenic differentiation of BMSCs, while overexpression of SIRT1 reversed the effects of NEAT1 knockdown. Similarly, NEAT1 knockdown altered the inhibitory effect of carvacrol on osteolysis in vivo. Conclusion: Our research results demonstrate that carvacrol showed potential in treating osteolysis in aged mice by regulating NEAT1 to promote the expression of SIRT1 and can facilitate the osteogenic differentiation of BMSCs.

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“…Upregulation of NRF2 has been suggested as a mechanism for reduced cellular senescence in models of diseases such as osteoporosis [ 180 ], age-related macular degeneration [ 181 ], age-related cognitive decline [ 182 ] and renal fibrosis [ 183 ]. Recently, Liu et al described how NRF2 is activated during DOX-induced senescence in two human cancer cell lines and in vivo by an accumulation of the oncogene iASPP (Inhibitor of Apoptosis Stimulating Protein of P53), which binds and inhibits KEAP1 [ 184 , 185 ].…”

Section: Drug-induced Cardiotoxicity and The Role Of Nrf2mentioning

confidence: 99%

Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling

Roberts

Rainbow

Sharma

2023

IJMS

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Cardiovascular toxicity and diseases are phenomena that have a vastly detrimental impact on morbidity and mortality. The pathophysiology driving the development of these conditions is multifactorial but commonly includes the perturbance of reactive oxygen species (ROS) signalling, iron homeostasis and mitochondrial bioenergetics. The transcription factor nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2), a master regulator of cytoprotective responses, drives the expression of genes that provide resistance to oxidative, electrophilic and xenobiotic stresses. Recent research has suggested that stimulation of the NRF2 signalling pathway can alleviate cardiotoxicity and hallmarks of cardiovascular disease progression. However, dysregulation of NRF2 dynamic responses can be severely impacted by ageing processes and off-target toxicity from clinical medicines including anthracycline chemotherapeutics, rendering cells of the cardiovascular system susceptible to toxicity and subsequent tissue dysfunction. This review addresses the current understanding of NRF2 mechanisms under homeostatic and cardiovascular pathophysiological conditions within the context of wider implications for this diverse transcription factor.

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Eldecalcitol prevented OVX-induced osteoporosis through inhibiting BMSCs senescence by regulating the SIRT1-Nrf2 signal

Cited by 12 publications

References 59 publications

ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis

ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis

Carvacrol induces osteogenic differentiation of BMSCs and alleviates osteolysis in aged mice by upregulating lncRNA NEAT1 to promote SIRT1 expression

Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling

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