An osteoinductive effect of phytol on mouse mesenchymal stem cells (C3H10T1/2) towards osteoblasts

Sanjeev, Ganesh; Sidharthan, D. Saleth; Pranavkrishna, S.; Pranavadithya, S.; Abhinandan, R.; Akshaya, R.L.; Balagangadharan, K.; Siddabathuni, Nishitha; Srinivasan, Swathi; Selvamurugan, N.

doi:10.1016/j.bmcl.2020.127137

Cited by 17 publications

(7 citation statements)

References 39 publications

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“…MiR-21, largely known for its regulatory role in bone [112], induces BM-MSC bone regeneration through the SMAD7-SMAD1/5/8-RUNX2 pathway [107]. The link between miR-21a and SMAD7 was confirmed by a very recent study, demonstrating that phytol, derived from aromatic plants, is able to promote osteoblast differentiation in C3H10T1/2 cells by downregulating SMAD7 through miR-21a, thus leading to the increased expression of RUNX2 [113]. Similarly, the expression of miR-21-5p was also increased and associated with a reduced expression of SMAD7 during the pulsed electromagnetic field (PEMF)induced osteogenic differentiation of human BM-MSCs, stimulating the TGF-β signaling pathway [114].…”

Section: Tgf-β/bmp Signaling Pathway Intracellular and Extracellular mentioning

confidence: 87%

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

Mazziotta

Lanzillotti

Iaquinta

et al. 2021

IJMS

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Mesenchymal stem cells (MSCs) have been identified in many adult tissues and they have been closely studied in recent years, especially in view of their potential use for treating diseases and damaged tissues and organs. MSCs are capable of self-replication and differentiation into osteoblasts and are considered an important source of cells in tissue engineering for bone regeneration. Several epigenetic factors are believed to play a role in the osteogenic differentiation of MSCs, including microRNAs (miRNAs). MiRNAs are small, single-stranded, non-coding RNAs of approximately 22 nucleotides that are able to regulate cell proliferation, differentiation and apoptosis by binding the 3′ untranslated region (3′-UTR) of target mRNAs, which can be subsequently degraded or translationally silenced. MiRNAs control gene expression in osteogenic differentiation by regulating two crucial signaling cascades in osteogenesis: the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1(Wnt)/β-catenin signaling pathways. This review provides an overview of the miRNAs involved in osteogenic differentiation and how these miRNAs could regulate the expression of target genes.

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Section: Tgf-β/bmp Signaling Pathway Intracellular and Extracellular mentioning

confidence: 87%

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

Mazziotta

Lanzillotti

Iaquinta

et al. 2021

IJMS

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“…On top of that, three compounds have been reported to be involved in cell differentiation induction activity. The compounds mentioned are β-asarone, phytol and carvacrol, which were involved in the differentiation of neuron cells, osteoblast and endothelial cells, respectively [ 33 , 39 , 40 ]. Although there are only three compounds that are associated with cell differentiation activity, the presence of the other compounds in the extract is worth taking note of, as there are studies that have reported that the biological activities of plant-derived products are contributed to by the synergistic effect between compounds [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Potential and Bioactive Profiles of Piper sarmentosum Ethanolic Extract-Treated Stem Cells

et al. 2023

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Piper sarmentosum is a well-known traditional herbal plant in various diseases treatments. Multiple scientific studies have also reported various biological activities exhibited by the plant’s extract, such as antimicrobial, anticarcinogenic and antihyperglycemic activities, and, in addition, a bone protective effect in ovariectomized rats has been reported. However, no known Piper sarmentosum extract is involved in osteoblast differentiation using stem cells. Our study aims to identify the potential of P. sarmentosum ethanolic extract to induce osteoblast differentiation of human peripheral blood stem cells. Prior to the assay, the proliferation ability of the cells was observed for 14 days and the presence of hematopoietic stem cells in the culture was determined by the expression of SLAMF1 and CD34 genes. During the differentiation assay, the cells were treated with P. sarmentosum ethanolic extract for 14 days. Osteoblast differentiation was examined using an (alkaline phosphatase) ALP assay, by monitoring the expression of osteogenic gene markers and by von Kossa staining. The untreated cells served as the negative control, while cells treated with 50 µg/mL ascorbic acid and 10 mM β-glycerophosphate acted as the positive control. Finally, the determination of the compound profile was performed using a gas chromatography-mass spectrometry (GC-MS) analysis. The isolated cells were able to proliferate for 14 days during the proliferation assay. The expression of hematopoietic stem cell markers was also upregulated during the 14 days assay. Following the differentiation induction, the ALP activity exhibited a significant increase (p < 0.05) from day 3 of the differentiation assay. A molecular analysis also showed that the osteogenic markers ALP, RUNX2, OPN and OCN were upregulated compared to the positive control. The presence of mineralized cells with a brownish-stained morphology was observed, indicating the mineralization process increased in a time-dependent manner regardless of the concentration used. There were 54 compounds observed in the GC-MS analysis, including β-asarones, carvacrol and phytol, which have been shown to possess osteoinductive capacities. Our results demonstrate that the ethanolic extract of P. sarmentosum can induce osteoblast differentiation of peripheral blood stem cells. The extract contains potent compounds which can potentially induce the differentiation of bone cells, i.e., osteoblasts.

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“…MiR-21 was also upregulated during osteogenic differentiation in murine multilineage cells (MMCs) induced by BMP-9, and miR-21 overexpression was found to sustain the activation of BMP-9-Smad1/5/8 signalling by directly inhibiting Smad7 [ 257 ]. Additionally, syringic acid treatment in mouse MSCs [ 258 ] and phytol treatment in C3H10T1/2 cells [ 259 ] were found to stimulate osteogenic differentiation through the miR-21-mediated downregulation of Smad7 , which, in turn, activated RUNX2 expression.…”

Section: Microrna Regulation Of the Smad Cascadesmentioning

confidence: 99%

Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review

Loh

Norman

Lai

et al. 2023

IJMS

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MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3′-untranslated regions (3′-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/β-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-βs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-β/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science.

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An osteoinductive effect of phytol on mouse mesenchymal stem cells (C3H10T1/2) towards osteoblasts

Cited by 17 publications

References 39 publications

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

Osteogenic Potential and Bioactive Profiles of Piper sarmentosum Ethanolic Extract-Treated Stem Cells

Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review

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