Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence

Geng, Qinghe; Gao, Haiyan; Yang, Renlei; Guo, Kaijin; Miao, Dengshun

doi:10.7150/ijbs.25783

Cited by 94 publications

(98 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comelekoglu et al found that BMD was reduced in 14% of OVX rats compared to control rats [29]. Moreover, accumulated evidences proved that osteoporosis was usually accompanied by weight gain [30,31]. Similar to these reports, we found that the body weight of OVX rats was elevated without altering food intake.…”

Section: Discussionsupporting

confidence: 87%

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

et al. 2020

View full text Add to dashboard Cite

Objective: Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis by activating the estrogen receptor. Research has shown that resveratrol exhibits some type of estrogen receptor agonist activity, reducing the risk of breast cancer. However, its mechanism of action remains largely unknown. This study aims to investigate the effect of resveratrol on osteoblastic and osteoclastic differentiation and its potential role in the regulation of autophagy. Methods: Sprague Dawley (SD) rats underwent ovariectomies (OVX) and were administered resveratrol (at 10, 20 or 40 mg/kg/d) for 8 weeks. The calcium content and the bone mineral density (BMD) were measured in the lumbar vertebrae (L3) and the right distal femur-tibia bone region. The osteoblasts and osteoclasts were isolated from rat lumbar vertebrae by enzyme digestion and bone marrow induction, respectively. The cells were then cultured with resveratrol in combination with bafilomycin or leupeptin to inhibit or activate autophagy, respectively. Western blotting was used to assess the differentiation markers and autophagy-related genes in the osteoblasts and osteoclasts. Results: Compared to the sham group, the bone calcium content and BMD were significantly decreased in the OVX group (p < 0.05), while resveratrol attenuated these in a dose-dependent manner. In the osteoblasts, vascular endothelial growth factor (VEGF), and alpha-1 type I collagen (COL1A1) were markedly decreased, and in osteoclasts, the receptor activator of nuclear factor-κB ligand (RANKL) was increased in the OVX group, while resveratrol reversed this pattern in a dose-dependent manner. The inhibition of autophagy in osteoblasts and its activation in osteoclasts was observed in the OVX group. However, with resveratrol, this was reversed in a dosedependent manner. Conclusion: Overall, resveratrol promotes osteoblastic differentiation and suppresses osteoclastic differentiation in a rat model with postmenopausal osteoporosis by regulating autophagy.

show abstract

Section: Discussionsupporting

confidence: 87%

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

et al. 2020

View full text Add to dashboard Cite

show abstract

“…1 Oxidative stress (OS) plays an important role in decreasing osteogenic differentiation in cell lines and the bone mineral density during age-related osteoporosis. 2,3 Plasma antioxidant levels significantly decrease in women with age-related osteoporosis. 4 Mesenchymal stem cells (MSCs) can induce repair processes at sites of injury in vivo by replenishing bone cells, including chondrocytes and osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

Selenium Nanoparticles by Moderating Oxidative Stress Promote Differentiation of Mesenchymal Stem Cells to Osteoblasts

Fatima¹,

Alfrayh²,

Alrashed³

et al. 2021

IJN

View full text Add to dashboard Cite

“…Naturally occurring plant-based compounds have been known to harbor therapeutic properties including osteogenesis. Phytoestrogens, which are naturally occurring non-steroidal plant compounds, are especially good candidates given their ability to exert beneficial agonistic effects on alleviating menopausal symptoms and bone loss ( Dutertre and Smith, 2000 ; Lv et al, 2018 ; Geng et al, 2019 ; Zhou et al, 2020 ), without increasing estrogenic cancer risks ( Adlercreutz, 2002 ; Horn-Ross et al, 2003 ; Anderson et al, 2013 ; Yang et al, 2019 ). Reports on the osteogenic agonism of individual phytoestrogens have been varied, ranging from strong agonism to antagonism with induction of adipogenesis even for the same compound despite the structural similarity to estrogen ( Dang and Lowik, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

A Rapid and Highly Predictive in vitro Screening Platform for Osteogenic Natural Compounds Using Human Runx2 Transcriptional Activity in Mesenchymal Stem Cells

Wang

Lee

Bai

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The rapid aging of worldwide populations had led to epidemic increases in the incidence of osteoporosis (OP), but while treatments are available, high cost, adverse effects, and poor compliance continue to be significant problems. Naturally occurring plant-based compounds including phytoestrogens can be good and safe candidates to treat OP, but screening for osteogenic capacity has been difficult to achieve, largely due to the requirement of using primary osteoblasts or mesenchymal stem cells (MSCs), the progenitors of osteoblasts, to conduct time-consuming in vitro and in vivo osteogenic assay. Taking advantage of MSC osteogenic capacity and utilizing a promoter reporter assay for Runx2, the master osteogenesis transcription factor, we developed a rapid in vitro screening platform to screen osteogenic small molecules including natural plant-based compounds. We screened eight plant-derived compounds from different families including flavonoids, polyphenolic compounds, alkaloids, and isothiocyanates for osteogenic capacity using the human RUNX2-promoter luciferase reporter (hRUNX2-luc) transduced into the mouse MSC line, C3H10T1/2, with daidzein—a well-studied osteogenic phytoestrogen—as a positive control. Classical in vitro and in vivo osteogenesis assays were performed using primary murine and human bone marrow MSCs (BMMSCs) to validate the accuracy of this rapid screening platform. Using the MSC/hRUNX2-luc screening platform, we were able not only to shorten the selection process for osteogenic compounds from 3∼4 weeks to just a few days but also simultaneously perform comparisons between multiple compounds to assess relative osteogenic potency. Predictive analyses revealed nearly absolute correlation of the MSC/hRUNX2-luc reporter platform to the in vitro classical functional assay of mineralization using murine BMMSCs. Validation using human BMMSCs with in vitro mineralization and in vivo osteogenesis assays also demonstrated nearly absolute correlation to the MSC/hRUNX2-luc reporter results. Our findings therefore demonstrate that the MSC/hRUNX2 reporter platform can accurately, rapidly, and robustly screen for candidate osteogenic compounds and thus be relevant for therapeutic application in OP.

show abstract

Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence

Cited by 94 publications

References 49 publications

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

Selenium Nanoparticles by Moderating Oxidative Stress Promote Differentiation of Mesenchymal Stem Cells to Osteoblasts

A Rapid and Highly Predictive in vitro Screening Platform for Osteogenic Natural Compounds Using Human Runx2 Transcriptional Activity in Mesenchymal Stem Cells

Contact Info

Product

Resources

About