MicroRNAs: Key Regulators to Understand Osteoclast Differentiation?

Lozano, Claire; Duroux-Richard, Isabelle; Firat, Hüseyin; Schordan, Eric; Apparailly, Florence

doi:10.3389/fimmu.2019.00375

Cited by 44 publications

(31 citation statements)

References 109 publications

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“…Suppression of miR-21 was associated with upregulation of osteoclast suppressor programmed cell death protein 4 (PDCD4), and downregulation of osteoclast marker cathepsin K (CTSK) [15]. Thus, miR-21 may be involved in bone biology, not only via promoting mobilization of osteoblast precursors, but also by regulation of osteoclast survival and differentiation [16]. It was also shown that miR-21 knockout mice are characterized by normal skeletal phenotype during development and maintain osteoblastogenesis in vivo.…”

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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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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“…15 The functions of several miRNAs in the bone regeneration process have already been investigated. [16][17][18] MiR-26a has been confirmed to regulate multiple pathways of osteogenic differentiation and promote bone restoration. 19,20 However, in the context of miRNA therapy, negatively charged miRNAs are ineffective in penetrating the cell membranes that are also negatively charged.…”

Section: Introductionmentioning

confidence: 99%

<p>Effects of miR-26a on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by a Mesoporous Silica Nanoparticle - PEI - Peptide System</p>

Yan¹,

Lü²,

Zhu³

et al. 2020

IJN

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Introduction: RNA-based therapy for bone repair and regeneration is a highly safe and effective approach, which has been extensively investigated in recent years. However, the molecular stability of RNA agents still remains insufficient for clinical application. High porosity, tunable size, and ideal biodegradability and biosafety are a few of the characters of mesoporous silicon nanoparticles (MSNs) that render them a promising biomaterial carrier for RNA treatment. Materials and Methods: In this study, a novel miR-26a delivery system was constructed based on MSNs. Next, we assessed the miRNA protection of the delivery vehicles. Then, rat bone marrow mesenchymal stem cells (rBMSCs) were incubated with the vectors, and the transfection efficiency, cellular uptake, and effects on cell viability and osteogenic differentiation were evaluated. Results: The results demonstrated that the vectors protected miR-26a from degradation in vitro and delivered it into the cytoplasm. A relatively low concentration of the delivery systems significantly increased osteogenic differentiation of rBMSCs. Conclusion: The vectors constructed in our study provide new methods and strategies for the delivery of microRNAs in bone tissue engineering.

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“…miR-16-5p was also shown to decline RANKL-induced osteoclast development. Collectively, these results proclaim that miR-16-5p blocks the process of osteoclastogenesis and this miRNA may act as a therapeutic target in case of giant cell tumor of bone [68][69][70].…”

Section: Micrornas In Gctbmentioning

confidence: 71%

Role of cancer stem cells in the development of giant cell tumor of bone

et al. 2020

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The primary bone tumor is usually observed in adolescence age group which has been shown to be part of nearly 20% of the sarcomas known today. Giant cell tumor of bone (GCTB) can be benign as well as malignant tumor which exhibits localized dynamism and is usually associated with the end point of a long bone. Giant cell tumor (GCT) involves mononuclear stromal cells which proliferate at a high rate, multinucleated giant cells and stromal cells are equally present in this type of tumor. Cancer stem cells (CSCs) have been confirmed to play a potential role in the development of GCT. Cancer stem cell-based microRNAs have been shown to contribute to a greater extent in giant cell tumor of bone. CSCs and microRNAs present in the tumors specifically are a great concern today which need indepth knowledge as well as advanced techniques to treat the bone cancer effectively. In this review, we attempted to summarize the role played by cancer stem cells involving certain important molecules/factors such as; Mesenchymal Stem Cells (MSCs), miRNAs and signaling mechanism such as; mTOR/PI3K-AKT, towards the formation of giant cell tumor of bone, in order to get an insight regarding various effective strategies and research advancements to obtain adequate knowledge related to CSCs which may help to focus on highly effective treatment procedures for bone tumors.

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MicroRNAs: Key Regulators to Understand Osteoclast Differentiation?

Cited by 44 publications

References 109 publications

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

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

<p>Effects of miR-26a on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by a Mesoporous Silica Nanoparticle - PEI - Peptide System</p>

Role of cancer stem cells in the development of giant cell tumor of bone

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