| First Author | Zhao SJ | Year | 2020 |
| Journal | J Bone Miner Res | Volume | 35 |
| Issue | 10 | Pages | 2015-2031 |
| PubMed ID | 32460388 | Mgi Jnum | J:297330 |
| Mgi Id | MGI:6478067 | Doi | 10.1002/jbmr.4099 |
| Citation | Zhao SJ, et al. (2020) Macrophage GIT1 Contributes to Bone Regeneration by Regulating Inflammatory Responses in an ERK/NRF2-Dependent Way. J Bone Miner Res 35(10):2015-2031 |
| abstractText | 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 GIT1(flox/flox) Lyz2-Cre (GIT1 CKO) mice, we observed that a GIT1 deficiency in the macrophages led to an exacerbation of interleukin 1beta (IL1beta) 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, IL1beta 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. (c) 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.. |
