Fatty acids derived from apoptotic chondrocytes fuel macrophages FAO through MSR1 for facilitating BMSCs osteogenic differentiation.

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate peroxisome proliferator-activated receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD+/SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments.

[Expression level and Clinical Significance of Serum SE-CAD and Matriptase in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To analyze the expression level of the serum soluble E cadherin (SE-CAD) and Matriptase and its clinical significance for evaluation of the disease condtions and prognosis in patients with acute myeloid leukemia (AML). METHODS: One hundred and ten patients diagnosed as AML in our hospital were divided into 3 groups: newly diagnosed group (38 cases), remission group (40 cases) and recurrence group (32 cases). The expression levels of serum matriptase were detected by Western blot, and the expression levels of serum SE-CAD were detected by ELISA. The serum levels of serum SE-CAD and matriptase among 3 groups were compared. Followin-up for one year, according to the outcome of patients, all the patients were divided into 2 groups: the survival group and death group. The serum levels of SE-CAD and Matriptase were compared between 2 groups. The correlation of serum levels of SE-CAD and matriptase with the survival of AML patients was analyzed by multivariate Logistic analysis. The evaluation value of the serum levels of SE-CAD and matriptase for the prognosis of the patients with AML were analyzed by receiver operating characteristic curves (ROC). RESULTS: The serum levels of SE-CAD and matriptase were siginificantly different among 3 groups (P＜0.05). The serum levels of SE-CAD and matriptase in remission group were lowest (P＜0.05), and the serum levels of SE-CAD and matriptase were not different between newly diagnoses and recurrence groups (P＞0.05). Multivariate Logistic analysis showed that the serum levels of SE-CAD and matriptase were independent risk factors for the prognosis of AML patients (OR=3.157, P＜0.05, OR=2.426, P＜0.05). By follow-up for 1 year, the serum expression levels of SE-CAD and Matriptase in survival group were lower than that in death group. ROC curve showed that when the cut-off value of matriptase level was 0.73 and SE-CAD level was 3.42 ng/ml, the AUC of predictions for the poor prognosis in AML patients was 0.849 (P＜0.05), the sensitivity was 85.6% (95%CI: 0.810~0.924) and specificity was 89.6% (95%CI: 0.849~0.941). CONCLUSION: The serum levels of SE-CAD and matriptase can perfectly evaluate the condition and short-term prognosis of the patients with AML.

The Fusarium Graminearum virulence factor FGL targets an FKBP12 immunophilin of wheat.

Wheat scab, caused by the fungal pathogen Fusarium graminearum is a devastating disease worldwide. Despite an extensive and coordinated effort to investigate this pathosystem, little progress has been made to understand the molecular basis of host-pathogen interactions, for example how the pathogen causes disease in plant. Recently, a secreted lipase (FGL1) has been identified from the fungus and shown to be an important virulence factor; however, the intrinsic function of FGL1 in plant is unknown. Here, we report the identification of the molecular components that may possibly be involved in the FGL virulence pathway using yeast two hybrid system. FGL gene was amplified from a local virulent strain (F15) and shown to be 99.5% identical to the original published FGL at the amino acid level. We showed that transient expression of this FGL gene by Agroinfiltration in tobacco leaves causes cell death further implicating the role of FGL in virulence. To identify FGL initial physical target in plant, we screened two wheat cDNA libraries using the FGL protein as the bait. From both libraries, a small FKBP-type immunophilin protein, designated wFKBP12, was found to physically interact with FGL. The direct interaction of FGL with wFKBP12 was confirmed in living onion epidermal cells by biomolecular fluorescence complementation (BiFC) assay. To investigate further, we then used wFKBP12 protein as bait and identified an elicitor-responsive protein that contains a potential Ca(2+) binding domain. Semi-quantitative PCR showed that this elicitor-responsive gene is down-regulated during the F. graminearum infection suggesting that this protein may be an important component in FGL virulence pathway. This work serves as an initial step to reveal how fungal lipases act as a general virulence factor.