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Current concepts of microRNA-mediated regulatory mechanisms in human pulp tissue-derived stem cells: a snapshot in the regenerative dentistry

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Abstract

One of the most studied class of non-coding RNAs is microRNAs (miRNAs) which regulate more than 60% of human genes. A network of miRNA gene interactions participates in stem cell self-renewal, proliferation, migration, apoptosis, immunomodulation, and differentiation. Human pulp tissue-derived stem cells (PSCs) are an attractive source of dental mesenchymal stem cells (MSCs) which comprise human dental pulp stem cells (hDPSCs) obtained from the dental pulp of permanent teeth and stem cells isolated from exfoliated deciduous teeth (SHEDs) that would be a therapeutic opportunity in stomatognathic system reconstruction and repair of other damaged tissues. The regenerative capacity of hDPSCs and SHEDs is mediated by osteogenic, odontogenic, myogenic, neurogenic, angiogenic differentiation, and immunomodulatory function. Multi-lineage differentiation of PSCs can be induced or inhibited by the interaction of miRNAs with their target genes. Manipulating the expression of functional miRNAs in PSCs by mimicking miRNAs or inhibiting miRNAs emerged as a therapeutic tool in the clinical translation. However, the effectiveness and safety of miRNA-based therapeutics, besides higher stability, biocompatibility, less off-target effects, and immunologic reactions, have received particular attention. This review aimed to comprehensively overview the molecular mechanisms underlying miRNA-modified PSCs as a futuristic therapeutic option in regenerative dentistry.

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Abbreviations

ASCs:

Adult stem cells

ALP:

Alkaline phosphatase

Bcl-2:

B cell lymphoma 2

Bcl-XL:

B cell lymphoma-extra-large

BMMSCs:

Bone marrow mesenchymal stem cells

BMP2:

Bone morphogenetic protein 2

BMPs:

Bone morphogenetic proteins

ceRNA:

Competing endogenous RNA

CircRNA:

Circular RNA

COLI:

Collagen type I

DSPP:

Dentin sialophosphoprotein

ERK1/2:

Extracellular signal-regulated protein kinase 1/2

ESCs:

Embryonic stem cells

FOXO1:

Forkhead box O1

HspB8:

Heat shock protein B8

IGF-1:

Insulin-like growth factor-1

IKBKB:

Nuclear factor kappa B kinase subunit beta

IL:

Interleukin

iPSCs:

Induced pluripotent stem cells

LncRNA:

Long non-coding RNA

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MiRNAs:

MicroRNAs

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MHS conceived the original idea, drafted the manuscript, and supervised the study. MHS, SN, MH, NM, ER, BA, and HKN wrote the manuscript and collected data. BA and MHS designed the figures. MHS edited and critically revised the manuscript for intellectual content. All listed authors read and approved the final manuscript.

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Soheilifar, M.H., Nobari, S., Hakimi, M. et al. Current concepts of microRNA-mediated regulatory mechanisms in human pulp tissue-derived stem cells: a snapshot in the regenerative dentistry. Cell Tissue Res 393, 229–251 (2023). https://doi.org/10.1007/s00441-023-03792-4

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