Shi Maobiao, Feng Jin, Chen Ping, Zhu Binsong, Sun Langlang, Ma Yaping, Zhang Yi, Wang Xin
Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, China.
Department of Clinical Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, China.
ACS Appl Mater Interfaces. 2025 Apr 16;17(15):22232-22244. doi: 10.1021/acsami.4c21489. Epub 2025 Apr 4.
Osteoporosis, a condition marked by reduced bone mass and structural deterioration, continues to be a major public health concern, especially as global populations age. Excessive osteoclast formation is a hallmark of osteoporosis. The transcription factor nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) is indispensable for the early differentiation of osteoclasts, orchestrating the expression of essential genes, while at the later stages, cathepsin K (CTSK) is essential for bone resorption activities of mature osteoclasts. Here, we fabricated ultrasound-responsive microdroplets (MDs) by modulating both the early stages of osteoclast differentiation and the functions of mature osteoclasts via targeting the NFATc1 and CTSK. The internalization of these dual MDs was evaluated in human bone marrow-derived mesenchymal stromal cells (hBMSCs) and murine RAW 264.7 macrophages, alongside the biocompatibility assay. Their effects on osteogenesis and osteoclastogenesis were further investigated , followed by analysis in osteoporotic rat models. The dual MDs exhibited a well-defined core-shell structure and demonstrated efficient cellular uptake with minimal cytotoxicity. Furthermore, dual MDs showed a minimal effect on the osteogenic differentiation of the hBMSCs. In osteoclastogenesis assays, dual MDs effectively suppressed both osteoclast differentiation and formation through a synergistic inhibitory effect. studies demonstrated that osteoporotic rats receiving dual MDs showed significant protection against bone loss induced by ovariectomy. These results highlight the potential of dual MDs as a sophisticated, targeted therapeutic approach to osteoporosis treatment.
骨质疏松症是一种以骨量减少和结构恶化为特征的疾病，仍然是一个主要的公共卫生问题，尤其是在全球人口老龄化的情况下。破骨细胞过度形成是骨质疏松症的一个标志。活化T细胞胞质1核因子（NFATc1）转录因子对于破骨细胞的早期分化不可或缺，它协调关键基因的表达，而在后期，组织蛋白酶K（CTSK）对于成熟破骨细胞的骨吸收活动至关重要。在这里，我们通过靶向NFATc1和CTSK来调节破骨细胞分化的早期阶段和成熟破骨细胞的功能，从而制造出超声响应性微滴（MDs）。在人骨髓间充质基质细胞（hBMSCs）和小鼠RAW 264.7巨噬细胞中评估了这些双微滴的内化情况，并进行了生物相容性测定。进一步研究了它们对成骨和破骨细胞生成的影响，随后在骨质疏松大鼠模型中进行了分析。双微滴呈现出明确的核壳结构，并显示出高效的细胞摄取且细胞毒性最小。此外，双微滴对hBMSCs的成骨分化影响最小。在破骨细胞生成试验中，双微滴通过协同抑制作用有效地抑制了破骨细胞的分化和形成。研究表明，接受双微滴的骨质疏松大鼠对卵巢切除诱导的骨质流失具有显著的保护作用。这些结果突出了双微滴作为一种复杂的、靶向性骨质疏松症治疗方法的潜力。
