Mesenchymal stem cells (MSCs), which are mechanosensitive cells, mediate the cells crosstalk in response to mechanical force, thereby playing a crucial role in bone homeostasis. Migrasomes serve as an important mediator for cellular communication. However, whether the mechanical stimulus regulates the biology and property of migrasomes on bone metabolism remains unknown. This study shows that mechanical stimulus could promote MSCs to synthesize and secrete migrasomes, which could significantly alleviate chronic infectious bone destruction in periodontal tissue by inhibiting osteoclastic differentiation of macrophage and reestablishing local immune microenvironment. Mechanistically, miR-29b-3p is more abundant in migrasomes from mechanical force stimulated MSCs than in control ones. MiR-29b-3p blocks the activation of pyrin domain containing protein 3 (NLRP3) and mitochondrial DNA (mtDNA) release by directly targeting on Tet1. Thus, mechanical sensing migrasomes inhibit osteoclast differentiation to alleviate inflammation induced bone destruction. These findings reveal that the mechanical stimulus controls the formation and properties of migrasomes, which provides a new biotechnological strategy for chronic infectious bone destruction intervention.