Bu Yang Huan Wu Prevents Osteogenic Effect of Muscle-Derived Stromal Cells via Regulating JAK/STAT Pathway

Abstract

Heterotopic ossification (HO) is a crucial pathological process in which bone or calcification develop in skeletal muscle and surrounding soft tissues. Muscle-derived stromal cells (MDSC) are important muscle-resident mesenchymal progenitor cells and macrophage-derived oncostatin M (OSM) can induce osteogenic differentiation. Bu Yang Huan Wu (BYHW), which has a long history of use in restraining inflammation, can prevent osteogenic differentiation and HO formation while underlying mechanism is still unclear. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is an important pathway to regulate osteogenic differentiation of related cells. In this study, we investigated whether BYHW could inhibit osteogenesis effect of MDSC through OSM mediated by macrophages, and whether JAK/STAT pathway regulated this biological process. We found that activated macrophages promoted osteogenic differentiation of MDSC through OSM and BYHW could decrease the level of OSM and osteogenic activity of MDSC. Further, we confirmed the regulatory effect of JAK/STAT pathway, blocking this pathway could suppress the level of OSM and osteogenic differentiation of MDSC. We showed that BYHW could suppress osteogenic differentiation of MDSC through JAK/STAT signalling. These findings expand the application scope of traditional Chinese medicine and provide a basis for the further investigation of the potential therapeutic role of HO.