A model for the dual role of BMPs in the entheseal stress hypothesis. As a reaction to local stress (damage, strain, and so on} BMP signaling can contribute to inflammation and ankylosis. Joint inflammation in the DBA/1 model is characterized by the presence of neutrophils which are attracted by BMP-induced chemokines. BMP-triggering of entheseal progenitor cells leads to new tissue formation and ankylosis in a complex cascade with multiple feedback mechanisms involving different molecular cascades. Pro-inflammatory cytokines such as TNF are known to stimulate BMPs in mesenchymal cell types and could provide another feedback system. Entheseal cell stress may also trigger other cascades leading to inflammation and tissue differentiation. BMP, bone morphogenetic protein; TNF, tumor necrosis factor.