Dental caries is a common oral disease that often causes severe pain and discomfort and may even lead to tooth loss. In severe and untreated cases, bacterial infection combined with the host’s immune response can lead to bone resorption, the destruction of bone tissue at the root of the tooth. In addition, traditional treatments for advanced dental caries, such as surgery, can result in bone defects that require complex bone grafting procedures.
Based on this, bone tissue engineering and tooth tissue regeneration have attracted the attention of researchers around the world. Recent studies have shown that microRNAs (miRNAs) – a class of non-coding small RNA sequences – play a key role in bone tissue regeneration. However, the underlying mechanisms and pathways of miRNA regulation remain unclear.
To explore the intrinsic process of tooth bone repair, a research team led by Associate Professor Nobuyuki Kawashima, graduate student Ziniu Yu and Professor Takashi Okiji of the Graduate School of Medicine and Dentistry, Tokyo Institute of Science, Japan, conducted a series of innovative experiments using human dental pulp stem cells (hDPSCs) and mice. Their research was published in the Journal of Translational Medicine, Volume 23, Issue 189, on February 16, 2025.
“hDPSCs are mesenchymal stem cells that can differentiate into odontoblasts or osteoblasts, which play a key role in dental tissue repair,” Kawashima explained. “In our study, we focused on a molecule called miRNA-27a, which we found to play an anti-inflammatory role by inhibiting the NF-κB pathway and may also promote tissue regeneration by activating the Wnt and BMP signaling pathways. By overexpressing miRNA-27a in hDPSCs, we explored how it directs these cells to differentiate into hard tissue-forming cells.”
Initially, the scientists used bioinformatics-based tools to study the effects of overexpressing miRNA-27a in hDPSCs. They identified dickkopf-related protein 3 (DKK3) and sclerostin domain-containing protein 1 (SOSTDC1) as the main target genes regulated by miRNA-27a.
In addition to DKK3 and SOSTDC1, other negative regulators of the wingless integration site family (Wnt) signaling pathway play key roles in the formation of new bone and tooth tissue. In addition, genes such as axis inhibitory protein 2 and adenomatous polyposis coli were also downregulated in hDPSCs overexpressing miRNA-27a. This suggests that miRNA-27a helps to release these biological “brakes” so that the cells can more effectively initiate osteogenic signals.
In addition to stimulating the Wnt pathway, miRNA-27a was also found to significantly affect the dentin/osteoblast differentiation of hDPSCs and activate the bone morphogenetic protein (BMP) pathway. The activation of the Wnt and BMP pathways suggests that the differentiation of hDPSCs promotes the formation of hard tissue-forming cells.
To validate their findings, the researchers transplanted collagen scaffolds containing hDPSCs expressing miRNA-27a into artificial defects in the mouse skull. Subsequent analysis showed that new bone-like tissue was formed, while this tissue was absent in the control group.
Kawashima concluded by highlighting the therapeutic potential of the study: “These results suggest that miRNA-27a may play a key role in promoting osteoid tissue formation. This opens up exciting possibilities for advancing regenerative therapies aimed at repairing dental and craniofacial defects.”
In conclusion, this study highlights the important translational potential of miRNA-27a in promoting dental tissue regeneration.
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