Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression

The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this study, single-cell RNA sequencing was used to identify immune cells in fracture tissues, including neutrophils, monocytes, T cells, B cells, and plasma cells. The number of B cells decreased significantly in the early stage of fracture healing. Furthermore, B cells in mice fracture models decreased significantly during the epiphyseal phase and then gradually returned to normal during the epiphyseal transformation phase of fracture healing. The B-cell pattern was opposite to that of bone formation and resorption activities. Notably, B-cell–derived exosomes inhibited bone homeostasis in fracture healing. In humans, a decrease in the number of B cells during the epiphyseal phase stimulated fracture healing. Then, as the numbers of osteoblasts increased during the callus reconstruction stage, the number of B cells gradually recovered, which reduced additional bone regeneration. Thus, B cells are key regulators of fracture healing and inhibit excessive bone regeneration by producing multiple osteoblast inhibitors.

The regulation of bone formation and detailed mechanisms are still largely elusive, and the roles of microRNAs in this process have attracted much attention. Recently, a specific subtype of CD31^hiendomucin^hi (CD31^hiEMCN^hi) endothelium has been identified to promote bone formation, together with osteoblast development. However, the role of microRNA143 in the generation of CD31^hi EMCN^hi endothelium and bone formation remains unknown. In this study, we found that miR-143 was expressed both in osteoblast cells and CD31^hiEMCN^hi endothelial cells. Serum miR-143 level was negatively correlated with age in humans. Overexpression of miR-143 promoted osteoblast formation and angiogenic effects. Furthermore, CD31^hiEmcn^hi vessels and osteoblast formation were significantly inhibited in miR-143 knockout mice. Mechanistically, inhibitor HDAC7 was directly targeted by miR-143 and knockdown of HDAC7 was found to rescue the function of miR-143 deficiency. Thus, miR-143 promotes angiogenesis coupling with osteoblast differentiation by targeting HDAC7, which may serve as a potential target in angiogenic and osteogenic diseases.

Background: Acute ischemic stroke (AIS) is the main cause of worldwide death and disability. Early neurological deterioration (END) can further increase the probability of death and disability in patients with ischemic stroke. Therefore, it is essential to find biomarkers to predict END early. Inflammatory response plays a crucial role in determining the course, outcome, and prognosis of END. Earlier studies focused on the relationship between routine hematological inflammatory markers and END, which limited the results. At present, relatively new and comprehensive markers of inflammatory response are relatively scarce. In this study, we investigate the predictive value of inflammatory markers in acute ischemic stroke cases for END which include systemic inflammatory response index (SIRI), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), and then to establish a nomogram model. Methods: A total of 375 patients with AIS were analyzed who were admitted to the Second Affiliated Hospital of Harbin Medical University from September 2019 to June 2021. The associations between END and inflammatory markers were studied by employing the analysis of univariate. Following that, through regression models of the least absolute shrinkage and selection operator, the END risk model’s feature selection was optimized. The development of the model of prediction was carried out by applying the multivariable logistic regression analysis. The calibration, discrimination, and clinical efficacy of the prediction model were studied via calibration plot, C-index, and decision curve analysis (DCA). The bootstrapping validation method was used for the evaluation of internal validation. Results: We constructed a nomogram consisting of CRP, monocytes, NIHSS and SIRI. This model had desirable calibration and discrimination, with a C-index of 0.757 (95% confidence interval: 0.702–0.805). Interval validation could still achieve the higher C-index value of 0.747. When the risk threshold for END was greater than 13% but less than 84%, DCA proved to be clinically useful. Conclusions: Our research shows that SIRI can be used as a new predictor of END, as well as a monitor of treatment response. Compared with the traditional single inflammatory indicator, the integration of SIRI nomogram can predict the occurrence of END more objectively and reliably.

Osteosarcoma is the most common type of primary malignant bone tumor, and deregulated microRNAs (miRNAs or miRs) in osteosarcoma have attracted great attention. In the present study, through miRNA microarray analysis, it was identified that miR-148a expression was significantly increased in osteosarcoma tissues. Increased miR-148a expression was significantly correlated with tumor progression and prognosis. Furthermore, increased miR-148a expression could promote osteosarcoma growth in vitro and in vivo, and the tumor-promoting effect was due to enhanced activation of the phosphoinositide 3-kinase signaling pathway caused by miR-148a-mediated inhibition of phosphatase and tensin homolog expression. Together, the present results suggest a role for miR-148a in osteosarcoma development and its potential use in prognosis prediction and cancer therapy.