Yang Wenbo, Pan Qing, Peng Yizhong, Hu Yuxiang, Cui Yongzhi, Shao Zengwu, Meng Chunqing, Wang Hong, Huang Wei
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
J Control Release. 2025 Apr 10;380:219-239. doi: 10.1016/j.jconrel.2024.12.081. Epub 2025 Feb 5.
Steroid-induced osteonecrosis of the femoral head (SANFH) is a common hip joint disease that imposes a heavy economic burden on society. Patients continue to experience bone necrosis even after discontinuing glucocorticoid therapy, and the specific mechanisms require further investigation. The results of this study demonstrate that exosomes secreted by damaged vascular endothelial cells in SANFH lesions may be a crucial factor leading to abnormal adipogenic differentiation of bone marrow stromal cells (BMSCs). We also found that adipogenically differentiated BMSCs can secrete increased pro-inflammatory factors, which contribute to the maintenance of endothelial cell damage, thereby creating a vicious cycle. Due to endothelial damage and abnormal differentiation of BMSCs, insufficient bone repair occurs, leading to spontaneous disease progression. Based on our newly explored mechanism, we designed a nanomaterial, M-SiO@Icariin@EBHM, that simultaneously targets the repair of damaged vascular endothelium and re-regulation of BMSCs, and we assessed its role in delaying SANFH progression. We found that the M-SiO@Icariin@EBHM nanomaterial can target SANFH lesions when applied systemically, effectively clearing the elevated reactive oxygen species in vascular endothelial cells caused by glucocorticoids and regulating the osteogenic differentiation of BMSCs. This process breaks the vicious cycle while promoting bone repair and significantly inhibiting SANFH progression, revealing its potential as a promising treatment strategy for SANFH.
类固醇诱导的股骨头坏死（SANFH）是一种常见的髋关节疾病，给社会带来沉重的经济负担。即使停用糖皮质激素治疗后，患者仍会持续出现骨坏死，其具体机制有待进一步研究。本研究结果表明，SANFH病变中受损血管内皮细胞分泌的外泌体可能是导致骨髓间充质干细胞（BMSC）异常成脂分化的关键因素。我们还发现，成脂分化的BMSC可分泌更多促炎因子，这有助于维持内皮细胞损伤，从而形成恶性循环。由于内皮损伤和BMSC异常分化，骨修复不足，导致疾病自发进展。基于我们新探索的机制，我们设计了一种纳米材料M-SiO@Icariin@EBHM，其可同时靶向受损血管内皮的修复和BMSC的重新调控，并评估了其在延缓SANFH进展中的作用。我们发现，M-SiO@Icariin@EBHM纳米材料全身应用时可靶向SANFH病变，有效清除糖皮质激素引起的血管内皮细胞中升高的活性氧，并调节BMSC的成骨分化。这一过程打破了恶性循环，同时促进骨修复并显著抑制SANFH进展，揭示了其作为SANFH一种有前景的治疗策略的潜力。
