Osteogenic commitment and differentiation of human mesenchymal stem cells by low‐intensity pulsed ultrasound stimulation

Costa, Viviana; Carina, Valeria; Fontana, Simona; Luca, Angela De; Monteleone, Francesca; Pagani, Stefania; Sartori, Maria; Setti, Stefania; Faldini, Cesare; Alessandro, Riccardo; Fini, Milena; Giavaresi, Gianluca

doi:10.1002/jcp.26058

Cited by 39 publications

(44 citation statements)

References 62 publications

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“…An interesting point in question was to determine the role of the miR-33a family in pre-osteoblast cells in order to identify a timeline of miR-33a-3p and miR-33a-5p expression during hMSCs osteoblast commitment. For this reason, we obtained pre-osteoblast cells by maintaining hMSCs in osteoblast medium [45], and a significant difference on miR-33a-3p and 5p expression patterns was evidenced ( Figure 4A). Surprisingly, the inhibition of miR-33a-5p on hMSCs maintenance in osteogenic medium induced an increase of miR-33a-3p expression, suggesting possible activation of a cell control mechanism from hMSCs to maintain a balance of miRNAs expression during the osteoblast differentiation process ( Figure 4B).…”

Section: Discussionmentioning

confidence: 99%

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Costa

Carina

Raimondi

et al. 2019

Cells

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Mesenchymal stromal cells (hMSCs) display a pleiotropic function in bone regeneration. The signaling involved in osteoblast commitment is still not completely understood, and that determines the failure of current therapies being used. In our recent studies, we identified two miRNAs as regulators of hMSCs osteoblast differentiation driving hypoxia signaling and cytoskeletal reorganization. Other signalings involved in this process are epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) signalings through the regulation of Yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression. In the current study, we investigated the role of miR-33a family as a (i) modulator of YAP/TAZ expression and (ii) a regulator of EGFR signaling during osteoblast commitments. Starting from the observation on hMSCs and primary osteoblast cell lines (Nh-Ost) in which EMT genes and miR-33a displayed a specific expression, we performed a gain and loss of function study with miR-33a-5p and 3p on hMSCs cells and Nh-Ost. After 24 h of transfections, we evaluated the modulation of EMT and osteoblast genes expression by qRT-PCR, Western blot, and Osteoimage assays. Through bioinformatic analysis, we identified YAP as the putative target of miR-33a-3p. Its role was investigated by gain and loss of function studies with miR-33a-3p on hMSCs; qRT-PCR and Western blot analyses were also carried out. Finally, the possible role of EGFR signaling in YAP/TAZ modulation by miR-33a-3p expression was evaluated. Human MSCs were treated with EGF-2 and EGFR inhibitor for different time points, and qRT-PCR and Western blot analyses were performed. The above-mentioned methods revealed a balance between miR-33a-5p and miR-33a-3p expression during hMSCs osteoblast differentiation. The human MSCs phenotype was maintained by miR-33a-5p, while the maintenance of the osteoblast phenotype in the Nh-Ost cell model was permitted by miR-33a-3p expression, which regulated YAP/TAZ through the modulation of EGFR signaling. The inhibition of EGFR blocked the effects of miR-33a-3p on YAP/TAZ modulation, favoring the maintenance of hMSCs in a committed phenotype. A new possible personalized therapeutic approach to bone regeneration was discussed, which might be mediated by customizing delivery of miR-33a in simultaneously targeting EGFR and YAP signaling with combined use of drugs.

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Section: Discussionmentioning

confidence: 99%

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Costa

Carina

Raimondi

et al. 2019

Cells

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“…LIPUS-stimulated MSC show an increase in hydroxyapatite content and in the release of type I collagen and osteopontin, and this seems to be additive to the use of osteogenic differentiation medium [ 45 ]. Human nucleus pulposus cells are a promising cell therapy source for intervertebral disc degeneration, and LIPUS promotes the production of type II collagen, aggrecan, and Sox9 in these cells in vitro.…”

Section: Biological Effects Of Ultrasoundmentioning

confidence: 99%

Ultrasound Therapy: Experiences and Perspectives for Regenerative Medicine

Lucas

Pérez

Bernal

et al. 2020

Genes

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Ultrasound has emerged as a novel tool for clinical applications, particularly in the context of regenerative medicine. Due to its unique physico-mechanical properties, low-intensity ultrasound (LIUS) has been approved for accelerated fracture healing and for the treatment of established non-union, but its utility has extended beyond tissue engineering to other fields, including cell regeneration. Cells and tissues respond to acoustic ultrasound by switching on genetic repair circuits, triggering a cascade of molecular signals that promote cell proliferation, adhesion, migration, differentiation, and extracellular matrix production. LIUS also induces angiogenesis and tissue regeneration and has anti-inflammatory and anti-degenerative effects. Accordingly, the potential application of ultrasound for tissue repair/regeneration has been tested in several studies as a stand-alone treatment and, more recently, as an adjunct to cell-based therapies. For example, ultrasound has been proposed to improve stem cell homing to target tissues due to its ability to create a transitional and local gradient of cytokines and chemokines. In this review, we provide an overview of the many applications of ultrasound in clinical medicine, with a focus on its value as an adjunct to cell-based interventions. Finally, we discuss the various preclinical and clinical studies that have investigated the potential of ultrasound for regenerative medicine.

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“…The results demonstrated that 10 ppm Ti ions could restrict the extension of osteoblast pseudopodia and inhibit cell spreading. osteoblast differentiation covers osteogenic commitment and osteogenic differentiation (45). during the osteogenic commitment process, runx2 is considered to be one of the core transcription factors (46), whilst alP and OSX are considered to be specific markers for the osteogenic differentiation process (47,48).…”

Section: Discussionmentioning

confidence: 99%

Role of MAPK/JNK signaling pathway on the regulation of biological behaviors of MC3T3‑E1 osteoblasts under titanium ion exposure

et al. 2020

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The oral cavity is a complex environment that is constantly undergoing remodeling. This provides a favorable electrolytic aqueous condition, which causes the corrosion of titanium implants and the release of titanium (Ti) ions. The accumulation of Ti ions in the peri-implant tissues may affect the osteogenesis process. Therefore, the present study aimed to investigate the possible effects of Ti ions on osteoblast physiology and its underlying mechanism, specifically the MaPK/JnK signaling pathway. in the present study, Mc3T3-e1 osteoblasts were cultured the medium containing 10 ppm Ti ions. confocal laser scanning microscopy was used to analyze cell morphology and adhesion. alkaline phosphatase (alP) activity assay and western blotting were performed to evaluate the expression of proteins associated with osteogenesis such as runx2 and osterix. nuclear translocation of JnK, a key factor of the MaPK signaling pathway, was visualized and analyzed using immunofluorescence staining. The results showed that 10 ppm Ti ions exerted negative effects on the biological behaviors of Mc3T3-e1 cells, which exhibited reduced adhesion, alP activity and osteogenic differentiation. it was also found that 10 ppm Ti ions activated the MaPK/JnK signaling pathway by promoting the nuclear translocation of JnK via phosphorylation. in addition, the inhibitory effects of 10 ppm Ti ions on Mc3T3-e1 cells was found to be reversed by the JnK inhibitor SP600125. in conclusion, the preset study suggests that the MaPK/JnK signaling pathway serves a key role in the molecular mechanism underlying the changes in osteoblast behavior following Ti ion exposure. These findings may serve as a valuable reference point for the further in-depth exploration of peri-implant bone loss.

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Osteogenic commitment and differentiation of human mesenchymal stem cells by low‐intensity pulsed ultrasound stimulation

Cited by 39 publications

References 62 publications

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Ultrasound Therapy: Experiences and Perspectives for Regenerative Medicine

Role of MAPK/JNK signaling pathway on the regulation of biological behaviors of MC3T3‑E1 osteoblasts under titanium ion exposure

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