Macrophages are multifunctional immune system cells that are essential for the mechanical stimulation‐induced control of metabolism. Piezo1 is a non‐selective calcium channel expressed in multifarious tissues to convey mechanical signals. Here, a cellular model of tension was used to study the effect of mechanical stretch on the phenotypic transformation of macrophages and its mechanism. An indirect co‐culture system was used to explore the effect of macrophage activation on bone marrow mesenchymal stem cells (BMSCs), and a treadmill running model was used to validate the mechanism in vivo for in vitro studies. p53 was acetylated and deacetylated by macrophages as a result of mechanical strain being detected by Piezo1. This process is able to polarize macrophages towards M2 and secretes transforming growth factor‐beta (TGF‐β1), which subsequently stimulates BMSCs migration, proliferation and osteogenic differentiation. Knockdown of Piezo1 inhibits the conversion of macrophages to the reparative phenotype, thereby affecting bone remodelling. Blockade of TGF‐β I, II receptors and Piezo1 significantly reduced exercise‐increased bone mass in mice. In conclusion, we showed that mechanical tension causes calcium influx, p53 deacetylation, macrophage polarization towards M2 and TGF‐β1 release through Piezo1. These events support BMSC osteogenesis.

Periodontitis is a chronic, inflammatory, and destructive disease caused by the imbalance of host immune response and dental biofilm, and has strong epidemiological and pathogenesis correlations with systemic diseases. The immune response in periodontitis involves both innate and adaptive immunity, with numerous immune cells and inflammatory pathways participating in a complex network of interactions. In the past decade, the concept of “trained immunity” has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. There is growing interest in exploring the role of trained immunity in chronic inflammatory and metabolic diseases such as atherosclerosis and diabetes mellitus. Evidence suggests that trained immunity may also regulate the onset and progression of periodontitis, serving as a bridge between periodontitis‐related comorbidities. In this review, we summarize concepts related to trained immunity and its development. Furthermore, we present current evidence that endorses the notion of trained immunity in periodontitis and analyze possible roles it may assume regarding periodontitis‐associated inflammatory reactions from a cellular perspective. Finally, we discuss various clinical therapeutic strategies for periodontitis and its associated comorbidities that target trained immunity. We hope that more researchers will pay attention to this emerging concept, thereby providing deeper insights into this novel field.

IntroductionDiabetic nephropathy (DN) has become a major public health burden in China. A more stable method is needed to reflect the different stages of renal function impairment. We aimed to determine the possible practicability of machine learning (ML)-based multimodal MRI texture analysis (mMRI-TA) for assessing renal function in DN.MethodsFor this retrospective study, 70 patients (between 1 January 2013 and 1 January 2020) were included and randomly assigned to the training cohort (n1 = 49) and the testing cohort (n2 = 21). According to the estimated glomerular filtration rate (eGFR), patients were assigned into the normal renal function (normal-RF) group, the non-severe renal function impairment (non-sRI) group, and the severe renal function impairment (sRI) group. Based on the largest coronal image of T2WI, the speeded up robust features (SURF) algorithm was used for texture feature extraction. Analysis of variance (ANOVA) and relief and recursive feature elimination (RFE) were applied to select the important features and then support vector machine (SVM), logistic regression (LR), and random forest (RF) algorithms were used for the model construction. The values of area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis were used to assess their performance. The robust T2WI model was selected to construct a multimodal MRI model by combining the measured BOLD (blood oxygenation level-dependent) and diffusion-weighted imaging (DWI) values.ResultsThe mMRI-TA model achieved robust and excellent performance in classifying the sRI group, non-sRI group, and normal-RF group, with an AUC of 0.978 (95% confidence interval [CI]: 0.963, 0.993), 0.852 (95% CI: 0.798, 0.902), and 0.972 (95% CI: 0.995, 1.000), respectively, in the training cohort and 0.961 (95% CI: 0.853, 1.000), 0.809 (95% CI: 0.600, 0.980), and 0.850 (95% CI: 0.638, 0.988), respectively, in the testing cohort.DiscussionThe model built from multimodal MRI on DN outperformed other models in assessing renal function and fibrosis. Compared to the single T2WI sequence, mMRI-TA can improve the performance in assessing renal function.

Background: Recent studies suggest that there is a potential connection between obstructive sleep apnea (OSA) and osteoporosis through dysregulation of bone metabolism. Orexin-A, a neuroprotective peptide secreted by the hypothalamus, is at a lower level in the plasma of OSA patients, which regulates appetite, energy expenditure and sleep-wake states. However, the protective effect of orexin-A on bone metabolism in OSA is unclear. Purpose: To investigate whether the activation of OX1R by orexin-A can reverse bone mass loss induced by chronic intermittent hypoxia (CIH). Methods: Mice were randomly divided into the normoxia group and CIH group. Within the CIH or normoxia groups, treatment groups were given a subcutaneous injection of either orexin-A or saline vehicle once every day for 4 weeks and then femurs were removed for micro-CT scans. Histology and immunohistochemical staining were performed to observe and calculate the changes in femurs as a result of hypoxia. Cell immunofluorescence and immunohistochemical staining were used to detect the expression of orexin receptors in MC3T3-E1 cells or in bones. CCK-8 assay, ALP assay kit and alizarin red staining were used to detect the viability, alkaline phosphatase (ALP) activity, and capacity of mineralization, respectively. The effect of orexin-A on osteogenic differentiation of MC3T3-E1 cells was evaluated using qRT-PCR, Western blot and cell staining. Results: CIH led to a decrease in the amount and density of trabecular bone, downregulated OCN expression while increasing osteoclast numbers in femurs and inhibited the expression of RUNX2, OSX, OPN and Nrf2 in MC3T3-E1 cells. Orexin-A treatment alleviated these CIH-induced effects by combining to OX1R. The level of HIF-1α was elevated both in CIH and orexin-A treatment groups. Conclusion: CIH environment inhibits osteogenesis and orexin-A can reverse bone mass loss induced by CIH through OX1R-Nrf2 /HIF-1α pathway.