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.

Curative efficacy and safety of traditional Chinese medicine xuebijing injections combined with ulinastatin for treating sepsis in the Chinese population: A meta-analysis.

BACKGROUND: Sepsis is a clinically critical disease. However, it is still controversial whether the combined use of traditional Chinese medicine Xuebijing injections (XBJI) and western medicine can enhance curative efficacy and ensure safety compared with western medicine alone. Thus, this research consisted of a systematic review of the curative efficacy and safety of traditional Chinese medicine XBJI combined with ulinastatin for treating sepsis in the Chinese population. METHODS: A total of 8 databases were retrieved: 4 foreign databases, namely, PubMed, The Cochrane Library, Embase, and Web of Science; and 4 Chinese databases, namely, Sino Med, China National Knowledge Infrastructure (CNKI), VIP, and Wangfang Data. The time span of retrieval began from the establishment of each database and ended on August 1, 2017. Published randomized controlled trials about the combined use of traditional Chinese medicine XBJI and western medicine were included, regardless of language. Stata12.0 software was used for statistical analysis. RESULTS: Finally, 16 papers involving 1335 cases were included. The result of meta-analysis showed that compared with the single use of ulinastatin, traditional Chinese medicine XBJI combined with ulinastatin could reduce the time of mechanical ventilation, shorten the length of intensive care unit (ICU) stay, improve the 28-day survival rate, and decrease the occurrence rate of multiple organ dysfunction syndrome, case fatality rate, procalcitonin (PCT) content, APACKEII score, tumor necrosis factor (TNF)-α level, and interleukin (IL)-6 level. CONCLUSION: On the basis of the common basic therapeutic regimen, the combined use of traditional Chinese medicine XBJI and ulinastatin was compared with the use of ulinastatin alone for treating sepsis in the Chinese population. It was found that the number of adverse events of combination therapy is not significantly increased, and its clinical safety is well within the permitted range. However, considering the limitations of this conclusion due to the low-quality articles included in the present research, it is necessary to conduct high-quality randomized controlled trials.