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Despite the best treatment, approximately 10% of fractures still face undesirable repair. Recently, many studies have focused on the importance of macrophages in bone repair; however, the cellular mechanisms by which they work are not yet fully understood. In this study, we explored the functions of macrophage G‐protein‐coupled receptor interacting protein 1 (GIT1) in healing a tibial monocortical defect model. Using GIT1flox/flox Lyz2‐Cre (GIT1 CKO) mice, we observed that a GIT1 deficiency in the macrophages led to an exacerbation of interleukin 1β (IL1β) production, more M1‐like macrophage infiltration, and impaired intramembranous ossification in vivo. The results of in vitro assays further indicated that the macrophage GIT1 plays a critical role in several cellular processes in response to lipopolysaccharide (LPS), such as anti‐oxidation, IL1β production alleviation, and glycolysis control. Although GIT1 has been recognized as a scaffold protein, our data clarified that GIT1‐mediated extracellular‐signal‐regulated kinase (ERK) phosphorylation could activate nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) in macrophages after LPS treatment. Moreover, we demonstrated that macrophage GIT1‐activated ERK/NRF2 negatively regulates the 6‐phosphofructo‐2‐kinase/fructose‐2, 6‐biphosphatase 3 (PFKFB3), facilitating the decrease of glycolysis. Our findings uncovered a previously unrecognized role of GIT1 in regulating ERK/NRF2 in macrophages to control the inflammatory response, suggesting that macrophage GIT1 could be a potential target to improve bone regeneration. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.. [ABSTRACT FROM AUTHOR]

Background: A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism.Methods: The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro.Results: In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons.Conclusions: Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition. [ABSTRACT FROM AUTHOR]

Increasing age negatively affects different phases of bone fracture healing. The present study aimed to explore underlying mechanisms related to bone fracture repair in the elderly. GSE17825 public transcriptome data from the Gene Expression Omnibus database were used for analysis. First, raw data were normalized and differentially expressed genes (DEGs) were identified. Next, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were implemented to evaluate pathways and DEGs. A protein–protein interaction (PPI) network was then constructed. A total of 726, 861, and 432 DEGs were identified between the young and elderly individuals at 1, 3, and 5 days after fracture, respectively. The results of GO, KEGG, and PPI network analyses suggested that the inflammatory response, Wnt signaling pathway, vascularization-associated processes, and synaptic-related functions of the identified DEGs are markedly enriched, which may account for delayed fracture healing in the elderly. These findings provide valuable clues for investigating the effects of aging on fracture healing but should be validated through further experiments. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a cause of disability. The present study aimed to investigate the molecular mechanisms involved in traumatic SCI. Transcriptome data under accession no. GSE5296, including 96 chips, were downloaded from the Gene Expression Omnibus database. The raw data were normalized and differentially expressed genes (DEGs) were identified. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analysis of up‑ and downregulated DEGs was performed. Additionally, a protein‑protein interaction network was constructed and the expression patterns of different genes were determined. Compared with sham samples, there were 374, 707, 1,322, 1,475, 1,724 and 1,342 DEGs identified at 0.5, 4, 24 and 72 h, and 7 and 28 days post‑injury, respectively. At 24 and 72 h, and 7 days following injury, the upregulated DEGs were markedly enriched in ‘inflammatory response’ and ‘immune process’. Downregulated DEGs were predominantly enriched in neuronal function‑associated pathways and ‘steroid biosynthesis’ process. Protein‑protein interaction network analysis demonstrated similar results. Trend charts further demonstrated that the inflammatory and neuronal functions were altered in a temporal and site‑specific manner. The present study provided an insight into the molecular mechanisms underlying traumatic SCI, which may benefit future SCI research and aid in therapy development. [ABSTRACT FROM AUTHOR]