CD36 inhibition promotes bone defect repair in spinal tuberculosis by regulating ferroptosis in bone marrow mesenchymal stem cells.

Spinal tuberculosis (STB) is commonly accompanied by progressive vertebral bone destruction and impaired bone repair. However, the key host mechanisms that limit bone regeneration in the tuberculous microenvironment remain unclear. Here, we demonstrate that bone marrow mesenchymal stem cells (BMSCs) derived from vertebrae of patients with STB display impaired osteogenic differentiation. We further demonstrate at the cellular level that ferroptosis is one of the key pathways mediating BMSC injury in the STB-associated infectious microenvironment. Combined transcriptomic analysis and functional validation reveal that CD36 knockdown markedly reduces lipid peroxidation and reactive oxygen species (ROS) accumulation, while also ameliorating ultrastructural damage. Mechanistically, CD36 downregulation suppresses FYN phosphorylation and reduces tyrosine phosphorylation of NRF2, thereby promoting NRF2 stabilization and accumulation, and ultimately enhancing cellular resistance to ferroptosis. In a mouse model of STB, pharmacological inhibition of CD36, activation of NRF2, or direct blockade of ferroptosis each alleviates trabecular bone destruction and restores osteogenic phenotypes. Taken together, our study elucidates a molecular mechanism underlying Mtb-induced impairment of osteogenesis in the vertebrae and identifies CD36-targeted attenuation of ferroptosis in BMSCs as a potential therapeutic strategy for bone repair in STB.