Orthodontic tooth movement is based on the remodeling of tooth-surrounding tissues in response to mechanical stimuli. During this process, human periodontal ligament cells (hPDLCs) play a central role in mechanosensing and mechanotransduction. Various in vitro models have been introduced to investigate the effect of tension on hPDLCs. They provide a valuable body of knowledge on how tension influences relevant genes, proteins, and metabolites. However, no systematic review summarizing these findings has been conducted so far. Aim of this systematic review was to identify all related in vitro studies reporting tension application on hPDLCs and summarize their findings regarding force parameters, including magnitude, frequency and duration. Expression data of genes, proteins, and metabolites was extracted and summarized. Studies’ risk of bias was assessed using tailored risk of bias tools. Signaling pathways were identified by protein-protein interaction (PPI) networks using STRING and GeneAnalytics. According to our results, Flexcell Strain Unit^® and other silicone-plate or elastic membrane-based apparatuses were mainly adopted. Frequencies of 0.1 and 0.5 Hz were predominantly applied for dynamic equibiaxial and uniaxial tension, respectively. Magnitudes of 10 and 12% were mostly employed for dynamic tension and 2.5% for static tension. The 10 most commonly investigated genes, proteins and metabolites identified, were mainly involved in osteogenesis, osteoclastogenesis or inflammation. Gene-set enrichment analysis and PPI networks gave deeper insight into the involved signaling pathways. This review represents a brief summary of the massive body of knowledge in this field, and will also provide suggestions for future researches on this topic.

This study aimed to investigate the effects of different magnitudes and durations of static tensile strain on human periodontal ligament cells (hPDLCs), focusing on osteogenesis, mechanosensing and inflammation. Static tensile strain magnitudes of 0%, 3%, 6%, 10%, 15% and 20% were applied to hPDLCs for 1, 2 and 3 days. Cell viability was confirmed via live/dead cell staining. Reference genes were tested by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and assessed. The expressions of TNFRSF11B, ALPL, RUNX2, BGLAP, SP7, FOS, IL6, PTGS2, TNF, IL1B, IL8, IL10 and PGE2 were analyzed by RT-qPCR and/or enzyme-linked immunosorbent assay (ELISA). ALPL and RUNX2 both peaked after 1 day, reaching their maximum at 3%, whereas BGLAP peaked after 3 days with its maximum at 10%. SP7 peaked after 1 day at 6%, 10% and 15%. FOS peaked after 3 days with its maximum at 3%, 6% and 15%. The expressions of IL6 and PTGS2 both peaked after 1 day, with their minimum at 10%. PGE2 peaked after 1 day (maximum at 20%). The ELISA of IL6 peaked after 3 days, with the minimum at 10%. In summary, the lower magnitudes promoted osteogenesis and caused less inflammation, while the higher magnitudes inhibited osteogenesis and enhanced inflammation. Among all magnitudes, 10% generally caused a lower level of inflammation with a higher level of osteogenesis.

Diabetes exacerbates the occurrence and severity of periodontitis, the pathogenesis of diabetic periodontitis (DPD) is influenced by the delayed resolution of inflammation. Eldecalcitol (ED-71) has shown promise in preventing bone loss in DPD. We herein aimed to investigate the role of ED-71 in the inflammatory regression phase of DPD and elucidate the underlying mechanisms. Type-2 diabetes was induced by streptozotocin injection in Wistar rats, and to explore the in vivo effect of ED-71 on macrophage efferocytosis, periodontitis was induced by ligation combined with lipopolysaccharide. Alveolar bone destruction was assessed using micro-computed tomography, hematoxylin-eosin, immunohistochemistry, and tartrate-resistant acid phosphatase staining. Immunofluorescence staining and flow cytometry detected neutrophils, apoptotic cells, and macrophage polarization in periodontal tissue. Additionally, flow cytometry, real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to examine macrophage efferocytosis and changes in store-operated calcium entry (SOCE). We found that rats with diabetes exhibited more severe alveolar bone destruction and increased neutrophil aggregates in periodontal tissue. Following the ED-71 administration, alveolar bone loss significantly decreased, and the immune microenvironment of periodontal tissue tended to suppress inflammation. Macrophages stimulated with high glucose experienced disruption of SOCE machinery, leading to the inhibition of efferocytosis in vitro. ED-71 demonstrated the ability to restore macrophage efferocytosis by correcting SOCE, and preventing sustained inflammatory damage to periodontal tissue. In conclusion, diabetes impairs macrophage efferocytosis and M2 polarization in periodontitis rats, resulting in the delayed resolution of inflammation. ED-71 could attenuate alveolar bone loss by mitigating macrophage via SOCE machinery in DPD.

Purpose: Sleep apnea (SA), associated with absent neural output, is characterised by recurrent episodes of hypoxemia and repeated arousals during sleep, resulting in decreased sleep quality and various health complications. Mitochondrial DNA copy number (mtDNA-CN), an easily accessible biomarker in blood, reflects mitochondrial function. However, the causal relationship between mtDNA-CN and SA remains unclear. This study aimed to investigate the causality between mtDNA-CN and SA while identifying potential mediating brain imaging phenotypes (BIPs). Methods: Two-sample bidirectional Mendelian randomisation (MR) analysis was performed to estimate the causal relationship between mtDNA-CN and SA, with further validation using Bayesian framework-based MR analysis. A two-step approach was employed to evaluate causal relationships between BIPs, mtDNA-CN and SA, utilising the “product of coefficients” method to assess the mediating effects of BIPs. Multiple testing errors were corrected using the Benjamini–Hochberg method. Results: Genetically predicted mtDNA-CN had a negative causal effect on SA (OR = 0.859, 95% CI = 0.785– 0.939, P = 3.20× 10^{− 4}), whereas SA did not have a causal effect on mtDNA-CN (OR = 1.0056, 95% CI = 0.9954– 1.0159, P = 0.2825). Among 3935 BIPs, two features related to white matter microstructure served as partial mediators: the second eigenvalue from diffusion MRI data analysed by tract-based spatial statistics in the right posterior thalamic radiation, with a mediation proportion of 11.37% (P = 0.0450), and fractional anisotropy in the right sagittal stratum, with a mediation proportion of 12.79% (P = 0.0323). Conclusion: This study demonstrated a causal relationship between mtDNA-CN and SA, with specific brain white matter microstructure phenotypes potentially acting as mediators. These findings highlight the potential of mtDNA-CN as a biomarker for SA and underscore its relevance in guiding future therapeutic strategies targeting mitochondrial health and brain white matter microstructure.