RETRACTED ARTICLE: Kaempferol promotes proliferation, migration and differentiation of MC3T3-E1 cells via up-regulation of microRNA-101

Kwon

et al. 2020

IJMS

The seeds (nutmegs) of Myristica fragrans Houtt have been used as popular spices and traditional medicine to treat a variety of diseases. A phenolic compound, ((7S)-8′-(benzo[3′,4′]dioxol-1′-yl)-7-hydroxypropyl)benzene-2,4-diol (7-HYB) was isolated from the seeds of M. fragrans. This study aimed to investigate the anabolic effects of 7-HYB in osteogenesis and bone mineralization. In the present study, 7-HYB promotes the early and late differentiation of MC3T3-E1 preosteoblasts. 7-HYB also elevated cell migration rate during differentiation of the preosteoblasts with the increased phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2, p38, and JNK. In addition, 7-HYB induced the protein level of BMP2, the phosphorylation of Smad1/5/8, and the expression of RUNX2. 7-HYB also inhibited GSK3β and subsequently increased the level of β-catenin. However, in bone marrow macrophages (BMMs), 7-HYB has no biological effects in cell viability, TRAP-positive multinuclear osteoclasts, and gene expression (c-Fos and NF-ATc1) in receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. Our findings suggest that 7-HYB plays an important role in osteoblast differentiation through the BMP2 and β-catenin signaling pathway. It also indicates that 7-HYB might have a therapeutic effect for the treatment of bone diseases such as osteoporosis and periodontitis.

Section: Discussionmentioning

confidence: 99%

7-HYB, a Phenolic Compound Isolated from Myristica fragrans Houtt Increases Cell Migration, Osteoblast Differentiation, and Mineralization through BMP2 and β-catenin Signaling

Kwon

et al. 2020

IJMS

“…The rapid response of the sensory nerve in the pre-injury period may alter the pulp stem cell niche environment and activate hDPSCs to mobilize and differentiate toward the injury to form restorative dentin [Brown G, 2003;Tamura K, 2007]. When stimulated by external stimuli, the pulp nerve not only perceives the stimulus immediately but also, because of its plasticity, can directly release neurotransmitters and other effects on surrounding tissue cells and can also sprout and grow, changing the morphological structure and affecting surrounding tissue cells [ Wang Y, 2019;Wang HS, 2019]. This shows that the pulp nerve is closely related to pulp injury repair because, on the one hand, the injury stimulus leads to changes in the pulp nerve, which may be the initiating factor for pulp injury repair, and on the other hand, the pulp nerve regulates the various tissue cells related to pulp repair [Zhan C, 2021; Zaky SH, 2021; Caviedes-Bucheli J, 2021; Calland JW, 1997].…”

Section: Discussionmentioning

confidence: 99%

Stathmin regulates the proliferation and differentiation of inflammatory hDPSCs through canonical Wnt/β-catenin pathway

Zhang

Luo

et al. 2023

Preprint

Objective Dental pulp stem cells (DPSCs) proliferation and differentiation functions are the basis of pulp injury repair; however, the mechanism of DPSCs functional changes in inflammatory pulp injury is unclear. This study aimed to clarify the regulatory role and mechanism of stathmin protein in inflammatory DPSCs. Study design: Differentially expressed genes between inflamed and healthy dental pulp were first analyzed using Gene Ontology (GO) enrichment. Next, human DPSCs were extracted and cultured in a differentiation medium with lipopolysaccharide (LPS). Stathmin was knocked down in LPS-DPSCs using lentivirus, and the Wnt/β-catenin activator LiCl was added. Stathmin- and LiCl-induced LPS-DPSCs and control cells were stained for alkaline phosphatase (ALP), alizarin red, and neuronal differentiation markers to observe mineralization and neuronal differentiation. Results Inflamed pulp revealed significantly lower expression of genes associated with cell proliferation, mineralization, and neuronal differentiation than healthy pulp. In stathmin knockout LPS-DPSCs, the expression levels of osteogenic-related genes were significantly reduced, and the neuronal differentiation capacity marker was decreased. Typical Wnt signaling has been studied in stathmin-deficient DPSCs. In contrast, the trend of osteogenic and neuronal differentiation of the cells rebounded significantly after adding LiCl, and the in vivo results also demonstrated the involvement of stathmin and LiCl in restorative dentin formation after pulp injury. Conclusions Our results depict that stathmin regulates the proliferation and differentiation of BMSCs while regulating cellular functions through the typical Wnt/β-catenin pathway, which provides new insights into the functional regulation of DPSCs.

Evidence-Based Complementary and Alternative Medicine

“…KP, a flavonoid identified in Drynariae Rhizoma , has been revealed to have beneficial effects on SOP via inhibiting osteoclast formation and bone loss [ 12 , 20 ]. Studies have illustrated that KP exerts the antiosteoporotic function via upregulating microRNA-101 and activating the Wnt/ β -catenin pathway, which promotes osteoblast differentiation, proliferation, and migration [ 21 ]. To further explore the mechanisms of KP in treating SOP, we carried out a series of bioinformatics analysis to screen potential targets and pathways in the present study.…”

Section: Discussionmentioning

confidence: 99%

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking

Tang

Zhang

Zhao

et al. 2022

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes ( p < 0.05 ), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways ( p < 0.05 ), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets’ active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets’ expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.