Metallofullerenol Promotes Osteogenic Differentiation Of Bone Marrow Stromal Cells Through BMP Signaling Pathway

[Gd@C₈₂（OH）₂₂]_nnanoparticles, a new type of polyhydroxylated endohedralMetallofullerenol nanoparticle, are attractive nanomaterials for its use in biomedicine due toits unique geometric structure and chemical properties. Existing literature showed that[Gd@C₈₂（OH）₂₂]_nnanoparticles have good anti-tumor activity. It has reported that[Gd@C₈₂（OH）₂₂]_nnanoparticles deposit in many tissues especially in bone of tumor-bearingmice. In that way, if and how the [Gd@C₈₂（OH）₂₂]_nnanoparticles affect the bone metabolismhave not been reported. On account of the question, we investigated the effects of[Gd@C₈₂（OH）₂₂]_nnanoparticles on the osteogenic and adipogenic differentiation by usingmodels of primary mouse bone marrow stromal cells （MSCs） and methods of CCK-8kit, ALPactivity assay, mineralized nodules formation and assay, red O stain and assay. Then westudied the BMP signaling pathway of osteogenic differentiation treated by [Gd@C₈₂（OH）₂₂]_nnanoparticles using western blot, real-time PCR, and immunofluorescence. Furthermore,Micro CT, and H&E staining were used to investigate the effect of [Gd@C₈₂（OH）₂₂]_nnanoparticles on the bone microstructure of osteoprosis models. Then ICP-MS was used toinvestigate the biodistribution of [Gd@C₈₂（OH）₂₂]_nin different tissues. The results showedthat:1.[Gd@C₈₂（OH）₂₂]_nnanoparticles could promote the proliferation and osteigenicdifferentiation, inhibit the adipogenic differentiation of MSCs.2. Through activate BMP signaling pathway,[Gd@C₈₂（OH）₂₂]_nnanoparticlesup-regulated the specific genes of osteogenic differentiation, promoted the osteogenicdifferentiation of MSCs.3.[Gd@C₈₂（OH）₂₂]_nnanoparticles could improve the bone microstructure ofosteoporosis rats, in favor of relieve the symptoms osteoporosis.In summary, we confirmed that [Gd@C₈₂（OH）₂₂]_nnanoparticles could activate the BMPsignaling pathway, promote the osteogenic differentiation of MSCs.