LAUSR

Knowledge of how the joint functions as an integrated unit in health and disease requires an understanding of the stromal cells populating the joint mesenchyme, including fibroblasts, tissue-resident macrophages and endothelial cells. Knowledge of the physiological and pathological mechanisms that involve joint mesenchymal stromal cells has begun to cast new light on why joint inflammation persists. The shared embryological origins of fibroblasts and endothelial cells might shape the behaviour of these cell types in diseased adult tissues. Cells of mesenchymal origin sustain inflammation in the synovial membrane and tendons by various mechanisms, and the important contribution of newly discovered fibroblast subtypes and their associated crosstalk with endothelial cells, tissue-resident macrophages and leukocytes is beginning to emerge. Knowledge of these mechanisms should help to shape the future therapeutic landscape and emphasizes the requirement for new strategies to address the pathogenic stroma and associated crosstalk between leukocytes and cells of mesenchymal origin.Stromal cells of mesenchymal origin can help to sustain inflammation in the joint by various mechanisms; understanding these mechanisms could inform new therapeutic strategies and explain why joint inflammation persists in diseases of the joint such as arthritis, enthesopathy and tendinopathy.Key pointsJoint inflammation and tissue damage are mediated by stromal cells of mesodermal origin.Stromal activation and memory of previous inflammatory insults are shared mechanisms exhibited by fibroblasts, tissue-resident macrophages and endothelial cells.Data characterizing the phenotype and function of cells of mesenchymal origin highlight the distinct fibroblast subtypes that mediate joint inflammation and tissue damage.Mesenchymal stromal cell niches and their interactions with leukocytes are implicated in the persistence of joint inflammation.For effective treatment of residual joint disease, strategies are needed that target the pathogenic stroma and associated immune cell crosstalk.