Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, PR China.
Department of Biochemistry, Shanxi Medical University, Basic Medical College, Taiyuan, 030001, PR China.
J Nanobiotechnology. 2024 May 17;22(1):261. doi: 10.1186/s12951-024-02436-1.
Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations. These challenges include issues associated with autologous material donor sites, intricate preparation procedures for artificial biomaterials, suboptimal biocompatibility, and extended degradation cycles, all of which are detrimental to bone regeneration. Hence, there is an urgent need to design a novel material with a straightforward preparation method that can substantially enhance bone regeneration. In this context, we developed a novel nanoparticle, mPPTMP195, to enhance the bioavailability of TMP195 for fracture treatment. Our results demonstrate that mPPTMP195 effectively promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts while inhibiting the differentiation of bone marrow mononuclear macrophages into osteoclasts. Moreover, in a mouse femur fracture model, mPPTMP195 nanoparticles exhibited superior therapeutic effects compared to free TMP195. Ultimately, our study highlights that mPPTMP195 accelerates fracture repair by preventing HDAC4 translocation from the cytoplasm to the nucleus, thereby activating the NRF2/HO-1 signaling pathway. In conclusion, our study not only proposes a new strategy for fracture treatment but also provides an efficient nano-delivery system for the widespread application of TMP195 in various other diseases.
骨折的延迟修复严重影响患者的健康，并显著增加经济负担。因此，临床上对有效治疗骨折的需求日益增长。虽然目前用于骨折修复的材料部分解决了骨完整性问题，但仍存在局限性。这些挑战包括与自体材料供体部位相关的问题、人工生物材料复杂的制备程序、较差的生物相容性和延长的降解周期，所有这些都不利于骨再生。因此，迫切需要设计一种具有简单制备方法的新型材料，可以显著增强骨再生。在这方面，我们开发了一种新型纳米颗粒 mPPTMP195，以提高 TMP195 用于骨折治疗的生物利用度。我们的结果表明，mPPTMP195 有效地促进骨髓间充质干细胞向成骨细胞分化，同时抑制骨髓单核巨噬细胞向破骨细胞分化。此外，在小鼠股骨骨折模型中，mPPTMP195 纳米颗粒与游离 TMP195 相比表现出更好的治疗效果。最终，我们的研究表明，mPPTMP195 通过阻止 HDAC4 从细胞质向细胞核易位，从而激活 NRF2/HO-1 信号通路，加速骨折修复。总之，我们的研究不仅提出了一种新的骨折治疗策略，还为 TMP195 在其他各种疾病中的广泛应用提供了高效的纳米递药系统。
