Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis

Abstract

Background and ObjectivesPeriodontitis is an immuno‐inflammatory disease caused by dental plaque biofilms and inflammations. The regeneration of bone tissue in inflammatory environment is of great significance for the treatment of periodontal disease, but the specific molecular mechanism of bone formation in periodontitis still needs further exploration. The objective of this study was to identify key osteogenesis‐related genes (ORGs) in periodontitis.MethodsWe used two datasets from the Gene Expression Omnibus (GEO) database to find differentially expressed mRNAs and miRNAs, further performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we predicted the downstream genes of the differentially expressed miRNAs (DEMs) by the TargetScan database and established a miRNA‐mRNA regulatory network. Finally, the osteogenic mechanism of periodontitis was explored through quantitative real‐time PCR (qRT‐PCR) by inducing inflammatory environment and osteogenic differentiation of hPDLSCs.ResultsThrough differential expression analysis and prediction of downstream target genes of DEMs, we created a miRNA‐mRNA regulatory network consisting of 29 DEMs and 11 differentially expressed osteogenesis‐related genes (DEORGs). In addition, the qRT‐PCR results demonstrated that BTBD3, PLAT, AKAP12, SGK1, and GLCE expression levels were significantly upregulated, while those of TIMP3, ZCCHC14, LIN7A, DNAH6, NNT, and ITGA6 were downregulated under the dual effects of inflammatory stimulation and osteogenic induction.ConclusionDEORGs might be important factors in the osteogenic phase of periodontitis, and the miRNA‐mRNA network may shed light on the clarification of the role and mechanism of osteogenesis in periodontitis and contribute to the development of novel therapeutic strategies.

Insights and Advancements in Periodontal Tissue Engineering and Bone Regeneration

“…The association of FGF-2 with heparin significantly decreases the degradation of FGF-2 and greatly enhances its mitogenic activity. Additionally, heparin sulfate proteoglycans act as cofactors in the interactions between FGF2 and FGF receptors, facilitating the activation of downstream signaling pathways [55][56][57]. In general, clinical data substantiates the safety and effectiveness of employing FGF-2 in the treatment of intraosseous defects in periodontal conditions.…”

“…This product incorporates β-tricalcium phosphate as a scaffold [50,51,55]. Residing within the ζ-granules of platelets and discharged upon activation, PDGF has been demonstrated to stimulate DNA synthesis, chemotaxis, and the synthesis of collagen and glycosaminoglycans in fibroblasts [56][57][58]. Laboratory analyses conducted in vitro have shown that PDGF significantly enhances the expression of stem cell markers and promotes the proliferation of mesenchymal stem cells (MSCs) isolated from PDL tissues [59].…”

Orally Derived Stem Cell-Based Therapy in Periodontal Regeneration: A Systematic Review and Meta-Analysis of Randomized Clinical Studies

“…A recent study assessed periodontal regenerative approaches in animal models, observing that mesenchymal stem cells used alone or mixed with other biomaterials, such as bovine bone, beta-tricalcium phosphate, or platelet-rich plasma, offered better regenerative outcomes than those of the group with biomaterials alone [42]. Most preclinical studies have indeed supported the biological rationale of employing MSCs to promote osteoinduction and tenogenesis, while simultaneously decreasing inflammation [26,[43][44][45].…”