Physical Exercise Modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p Expression in Progenitor Cells Promoting Osteogenesis

Valenti, Maria Teresa; Deiana, Michela; Cheri, Samuele; Dotta, Monica; Zamboni, Francesco; Gabbiani, Daniele; Schena, Federico; Carbonare, Luca Dalle; Mottes, Monica

doi:10.3390/cells8070742

Cited by 56 publications

(54 citation statements)

References 28 publications

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“…32 Thus, Smad4 expression is mediated by Smad4/Runx2 signaling at the transcriptional level, and Smad4 regulates Runx2 activity and the expression of other osteoblast genes in a feedback loop. 33,34 The cytoskeleton has been shown to control the activation of Smad4/Runx2 signaling in mesenchymal cells upon external stimulation, and cell morphology remodeling and cytoskeletal organization can affect stem cell lineage commitment. 14 Furthermore, the cytoskeletal network allows cells to transfer external mechanical stimuli into the nucleus and activates external stimuli-induced mechanotransduction transducers on the membrane.…”

Section: Introductionmentioning

confidence: 99%

<p>The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway</p>

Zhang¹,

Liu²,

Wang³

et al. 2020

IJN

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Background: In recent years, nanomaterials have been increasingly developed and applied in the field of bone tissue engineering. However, there are few studies on the induction of bone regeneration by tantalum nanoparticles (Ta NPs) and no reports on the effects of Ta NPs on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanisms. The main purpose of this study was to investigate the effects of Ta NPs on bone regeneration and BMSC osteogenic differentiation and the underlying mechanisms. Materials and Methods: The effects of Ta NPs on bone regeneration were evaluated in an animal experiment, and the effects of Ta NPs on osteogenic differentiation of BMSCs and the underlying mechanisms were evaluated in cell experiments. In the animal experiment, hematoxylin-eosin (HE) staining and hard-tissue section analysis showed that Ta NPs promoted bone regeneration, and immunohistochemistry revealed elevated expression of BMP2 and Smad4 in cells cultured with Ta NPs. Results: The results of the cell experiments showed that Ta NPs promoted BMSC proliferation, alkaline phosphatase (ALP) activity, BMP2 secretion and extracellular matrix (ECM) mineralization, and the expression of related osteogenic genes and proteins (especially BMP2, Smad4 and Runx2) was upregulated under culture with Ta NPs. Smad4 expression, ALP activity, ECM mineralization, and osteogenesis-related gene and protein expression decreased after inhibiting Smad4. Conclusion: These data suggest that Ta NPs have an osteogenic effect and induce bone regeneration by activating the BMP2/Smad4/Runx2 signaling pathway, which in turn causes BMSCs to undergo osteogenic differentiation. This study provides insight into the molecular mechanisms underlying the effects of Ta NPs in bone regeneration.

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Section: Introductionmentioning

confidence: 99%

<p>The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway</p>

Zhang¹,

Liu²,

Wang³

et al. 2020

IJN

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“…MiR-21 exogenously added to BMSCs cultures accelerated the osteogenesis process which resulted not only in increased expression of Runx-2, but also secretion of key osteogenic markers such as osteocalcin (OCL), osteopontin (OPN) and BMP-2. Valenti et al showed that miR-21, derived from sera collected from runners after intense exercise, had an anti-apoptotic effect on BMSCs and promoted their osteogenic potential by targeting PTEN and SMAD7 [13]. Moreover, miR-21 was shown to promote differentiation of MSCs derived not only from bone-marrow.…”

Section: Introductionmentioning

confidence: 99%

The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Śmieszek

Marcinkowska

Pielok

et al. 2020

Cells

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MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts’ differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

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“…Physical exercise has been reported to improve cognitive dysfunction by regulating miR-132 in AD [15]. A study by Valenti et al [16] supplied evidence that physical exercise increases the expression of miR-129-5p in progenitor cells promoting osteogenesis. Thus, we deduced that miR-129-5p might also be regulated by physical exercise in AD.…”

Section: Introductionmentioning

confidence: 99%

Physical Exercise Ameliorates the Cognitive Function and Attenuates the Neuroinflammation of Alzheimer’s Disease via miR-129–5p

Chen

Liu

et al. 2020

Dement Geriatr Cogn Disord

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Introduction: Physical exercise has a significant neuroprotective role in Alzheimer's disease (AD), but the underlying mechanisms remain elusive. Objective: This study aimed to explore the molecular mechanisms of physical exercise by analyzing the role of microRNA-129-5p (miR-129-5p) in AD mice and patients. Methods: AD mice and patients were treated with 4-week and 3-month physical exercise, respectively. The expression of miR-129-5p was measured using quantitative realtime PCR. The Morris water-maze test was used for cognition evaluation, and enzyme-linked immunosorbent assay was used for inflammation analysis. Results: In both AD mice and patients, the expression of miR-129-5p was elevated by physical exercise. By in vivo regulation of miR-129-5p, we found that the improved cognitive function and reduced inflammatory responses were reversed by the knockdown of miR-129-5p. In patients with AD, the serum expression of miR-129-5p was further found to be correlated with the serum levels of cognitive function markers and proinflammatory cytokines. Conclusion: All data indicated that the expression of miR-129-5p in AD mice and patients is significantly upregulated by physical exercise. The knockdown of miR-129-5p can abrogate the neuroprotective effect of exercise on cognition and neuroinflammation in AD mice. This study provides a novel insight into the molecular mechanisms underlying the neuroprotective effect of physical exercise in AD, and miR-129-5p may provide a novel therapeutic target for AD treatment.

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Physical Exercise Modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p Expression in Progenitor Cells Promoting Osteogenesis

Cited by 56 publications

References 28 publications

<p>The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway</p>

<p>The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway</p>

The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Physical Exercise Ameliorates the Cognitive Function and Attenuates the Neuroinflammation of Alzheimer’s Disease via miR-129–5p

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