MMP9 regulates the cellular response to inflammation after skeletal injury

article i nfo Likeothertissue injuries,bonefracturetriggersaninflammatoryresponse,whichplaysanimportantroleinskel- etalrepair.Inflammationisbelievedto havebothpositive and negative effects onbonerepair,butthe underlying cellular mechanisms are not well understood. To assess the role of inflammation on skeletal cell differentiation, weusedmousemodels offracturerepairthatstimulate eitherintramembranousorendochondral ossification. In the first model, fractures are rigidly stabilized leading to direct bone formation, while in the second model, frac- ture instability causes cartilage and bone formation. We compared the inflammatory response in these two me- chanical environments and found changes in the expression patterns of inflammatory genes and in the recruitment of inflammatory cells and osteoclasts. These results suggested that the inflammatory response could influence skeletal cell differentiation after fracture. We then exploited matrix metalloproteinase 9 (MMP9) that is expressed in inflammatory cells and osteoclasts, and which we previously showed is a potential regulator of cell fate decisions during fracture repair. Mmp9 �/� mice heal stabilized fractures via endochondral ossification, while wild type mice heal via intramembranous ossification. In parallel, we observed increases in macrophages and T cells in the callus of Mmp9