Single-cell analysis reveals OSM-mediated osteogenic differentiation in Kashin-Beck disease bone hyperplasia

Kashin-Beck Disease (KBD) is an endemic degenerative osteoarthropathy that was historically widespread across China. The disease is characterized by early-stage cartilage necrosis followed by late-stage bone hyperplasia and joint deformity. Although preventive measures like improved water sources and grain substitution have effectively controlled new pediatric cases, many advanced-stage patients still suffer from progressive bone hyperplasia without effective treatment options. Through single-cell RNA sequencing of clinical specimens from late-stage KBD, osteoarthritis and normal subchondral bone, we identified an expanded population of mesenchymal lineage cells with enhanced osteogenic differentiation potential in KBD. Cell communication analysis revealed significant activation of the oncostatin M (OSM) signaling pathway in KBD, which was validated by elevated expression of OSM in myeloid cells and its receptor in mesenchymal-osteoblastic cells. In vitro studies confirmed that T-2 toxin-stimulated RAW264.7 secreted OSM, which promoted osteogenic differentiation of BMSCs. Importantly, pharmacological inhibition of OSM effectively attenuated bone hyperplasia in a rat model of late-stage KBD.