bioinformatics-identification-candidate-biomarkers-associated-with

Bioinformatics Identification of Candidate Biomarkers Associated with Periodontitis in Cytokine-Treated Periodontal Ligament Stem Cells

The primary objective of the current study was to investigate the potential molecular mechanism underlying cytokine-induced periodontal ligament stem ...

The Second Affiliated Hospital of Harbin Medical University

Aspirin has positive effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. However, researchers did not give much thought to its effect on BMSCs adipogenic differentiation. Here, we analyzed the effect of aspirin on the BMSCs adipogenic differentiation. To detect whether the effect of aspirin on the adipogenic differentiation of BMSCs is associated with the disturbed epigenetic modification, the expression of histone deacetylases (HDACs), activity of HDACs and HAT, global histone H3 acetylation and H3k9 acetylation alterations were investigated. Moreover, to further explore and understand the binding mode between aspirin and HDACs, an attempt was made to identify the interaction between aspirin and the HDACs with the aid of in silico docking study. The results showed that aspirin could induce inhibition of BMSCs adipogenesis. The level of HDAC activity, global histone H3 acetylation, and H3k9 acetylation were all down regulated during adipogenic differentiation, and aspirin can reverse these decreases. Furthermore, the HDAC isoforms have different expression patterns in those progresses. The expression of HDAC9 was increased in a does-dependent manner when aspirin was introduced during BMSCs adipogenic differentiation. Docking study showed that high affinity of HDAC9 to aspirin was existed, suggesting that HDAC9 may has an important role in the process of aspirin-induced suppression of adipogenesis. Further studies are needed to define the intricate mechanisms of the HDAC isoforms, and all of these enable us to understand aspirin and its efficacy of inhibition of adipogenic differentiation and pave the way to aspirin clinical using for the tissue regenerating.

Aspirin-induced attenuation of adipogenic differentiation of bone marrow mesenchymal stem cells is accompanied by the disturbed epigenetic modification.

Human dental pulp stem cells (hDPSCs) possess self‑renewal and osteogenic differentiation properties, and have been used for orofacial bone regeneration and periodontal treatment. Aspirin has been demonstrated to enhance the regeneration of bone marrow mesenchymal stem cells (MSCs); however, the impact of aspirin on the osteogenic differentiation of hDPSCs remains unknown. In the present study, hDPSCs were characterized by flow cytometry, while their clonogenic potential and multipotency were assessed using alizarin red, Oil red O and alcian blue staining. The effect of aspirin on hDPSC viability was assessed using Cell Counting Kit‑8 assay. Osteogenic capacity was examined by alkaline phosphatase activity, alizarin red staining, reverse transcription‑polymerase chain reaction and western blotting. Furthermore, in vivo cranial defects were established in Sprague‑Dawley rats to evaluate the effect of aspirin on hDPSC‑based bone regeneration. Anorganic bovine bone was used as a bone replacement material and as the carrier for hDPSCs. New bone formation was observed through radiographic and histological analysis. The study demonstrated that hDPSCs expressed MSC markers and possessed multipotency in vitro. Aspirin was non‑toxic to hDPSCs at a concentration of ≤100 µg/ml and enhanced the osteogenesis of hDPSCs in vitro. Aspirin significantly increased hDPSC‑based bone formation in the rat cranial defect model at 8 or 12 weeks post‑implantation (P<0.05). The data suggested that aspirin promotes the osteogenic potential of hDPSCs in vitro and in vivo. Overall, the present study indicated that aspirin improves the bone regeneration capacity of hDPSCs.

Aspirin promotes osteogenic differentiation of human dental pulp stem cells.

Family with sequence similarity 20‑member C (FAM20C), a recently characterized Golgi kinase, performs numerous biological functions by phosphorylating more than 100 secreted proteins. However, the role of FAM20C in the salivary glands remains undefined. The present study demonstrated that FAM20C is mainly located in the cytoplasm of duct epithelial cells in the salivary glands. Fam20cf/f; Mmtv‑Cre mice were created in which Fam20c was inactivated in the salivary gland cells and observed that the number of ducts and the ductal cross‑sectional area increased significantly, while the number of acinar cells was reduced. The granular convoluted tubules (GCTs) exhibited an accumulation of aberrant secretory granules, along with a reduced expression and altered distribution patterns of β nerve growth factor, α‑amylase and bone morphogenetic protein (BMP) 4. This abnormality suggested that the GCT cells were immature and exhibited defects in developmental and secretory functions. In accordance with the morphological alterations and the reduced number of acinar cells, FAM20C deficiency in the salivary glands significantly decreased the salivary flow rate. The Na+, Cl- and K+ concentrations in the saliva were all significantly increased due to dysfunction of the ducts. Furthermore, Fam20c deficiency significantly increased BMP2 and BMP7 expression, decreased BMP4 expression, and attenuated the canonical and noncanonical BMP signaling pathways in the salivary glands. Collectively, the results of the present study demonstrate that FAM20C is a key regulator of acinar and duct structure and duct maturation and provide a novel avenue for investigating novel therapeutic targets for oral diseases including xerostomia.

Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice.

The influence of the knockout of gene Fam20a on mice salivary glands was studied in this research, to provide a potential gene therapeutic target for salivary gland dysfunction.

The effect and mechanism of gene Fam20a on the development and function of salivary glands in mice.

The family with sequence similarity 20-member C (FAM20C) kinase, a Golgi casein kinase, which is responsible for phosphorylating the majority of the extracellular phosphoproteins within S-x-E/pS motifs, and is fundamentally associated with multiple biological processes to maintain cell proliferation, biomineralization, migration, adhesion, and phosphate homeostasis. In dissecting how FAM20C regulates downstream molecules and potential mechanisms, however, there are multiple target molecules of FAM20C, particularly many phenomena remain elusive, such as changes in cell-autonomous behaviors, incompatibility in genotypes and phenotypes, and others.

Fam20c regulates the calpain proteolysis system through phosphorylating Calpasatatin to maintain cell homeostasis.

Behcet's syndrome, as a vasculitic disease involving multiple systems, often induces oral mucosal ulcers. However, levels of inflammatory cytokines and metabolites are unknown for the probability of developing the disease. This study aims to reveal the causal relationship between the cytokines and metabolites and Behcet's syndrome through Mendelian randomization analysis.

Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization.

Oral lichen planus (OLP) is a chronic immune-mediated inflammatory disease affecting the oral mucosa, with tongue lesions being clinically significant due to their association with oral cancer risk and taste dysfunction. However, the layer-specific molecular heterogeneity of the basal layer (BL), spinous layer (SL), and lamina propria (LP) in tongue OLP remains poorly characterized, limiting mechanistic understanding and therapeutic development.

Spatial Proteomics Reveals Layer-Specific Molecular Landscapes and KRT17-Mediated Inflammatory Crosstalk in Tongue Oral Lichen Planus.

Tongue squamous cell carcinoma (TSCC) is a common type of oral mucosal epithelial malignancy that can severely affect patient quality of life. Therefore, novel therapeutic strategies for TSCC are needed. This study aimed to investigate the role and mechanism of action of retinol-binding protein 4 (RBP4) in TSCC progression and its effect on tumor-associated macrophages. To this end, TSCC cell lines with RBP4 overexpression and knockdown were constructed, and effects of RBP4 expression on the proliferation and invasive abilities of TSCC cells were verified using ex vivo experiments. Furthermore, a tumor cell-macrophage co-culture model was established to assess the effect of RBP4 on macrophage polarization. RBP4 overexpression reduced the phosphorylation of the PI3K/Akt/mTOR pathway and inhibited tumor cell proliferation by regulating Snail levels; RBP4 inhibited TSCC cells from undergoing epithelial-mesenchymal transition. In addition, RBP4 promoted the activation of NF-κB signaling pathway, leading to macrophage polarization toward M1 type and inhibiting TSCC growth. We found for the first time that RBP4 affects the proliferation and migration of TSCC cells by inhibiting the activation of the PI3K-Akt signaling pathway, and that RBP4 promotes the M1-type polarization of tumor-associated macrophages, which contributes to their antitumor effects.

RBP4 interferes with tongue squamous cell carcinoma progression by inhibiting the PI3K/AKT signaling pathway and promoting macrophage M1-type polarization.

Article	Year
Aspirin-induced attenuation of adipogenic differentiation of bone marrow mesenchymal stem cells is accompanied by the disturbed epigenetic modification. The international journal of biochemistry & cell biology\| PubMed ID: 29471042	2018
Aspirin promotes osteogenic differentiation of human dental pulp stem cells. International journal of molecular medicine\| PubMed ID: 30085338	2018
Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice. International journal of molecular medicine\| PubMed ID: 30864688	2019
The effect and mechanism of gene Fam20a on the development and function of salivary glands in mice. Archives of oral biology\| PubMed ID: 35278791	2022
Fam20c regulates the calpain proteolysis system through phosphorylating Calpasatatin to maintain cell homeostasis. Journal of translational medicine\| PubMed ID: 37370126	2023
Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization. Cytokine\| PubMed ID: 39756125	2025
Spatial Proteomics Reveals Layer-Specific Molecular Landscapes and KRT17-Mediated Inflammatory Crosstalk in Tongue Oral Lichen Planus. The British journal of dermatology\| PubMed ID: 41640051	2026
RBP4 interferes with tongue squamous cell carcinoma progression by inhibiting the PI3K/AKT signaling pathway and promoting macrophage M1-type polarization. Scientific reports\| PubMed ID: 41699002	2026

Nan Miao

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