Niu Pingping, Zhao Liman, Yang Jing, Ding Yanan, Xu Xiaoqiao, Li Sijin, Song Lige, Chen Guosong, Sun Yao
Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Oral Implantology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, 200072, China.
The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
Adv Healthc Mater. 2025 Jan;14(3):e2402976. doi: 10.1002/adhm.202402976. Epub 2024 Dec 1.
Osteoporosis, a prevalent disease characterized by low bone density and increased fracture risk, poses significant health challenges for the elderly. Current treatments offer short-term benefits but are limited by long-term efficacy and adverse effects, highlighting the need for new strategies. Chondroitin sulfate polysaccharides (CS), a major component of the bone matrix, are crucial for bone and cartilage health. However, their role in osteoporosis is understudied due to the heterogeneity of natural CS. we found reduced CS levels in osteoporosis patients and developed CS4-NP, a self-assembled tetrasaccharide nanoparticle that mimics CS's structure. CS4-NP, which efficiently delivers the active CS4, significantly improves bone mass in ovariectomized osteoporosis models. It activates the Activating Transcription Factor 4-Cystathionine gamma-Lyase signaling axis in pre-osteoblasts, enhancing osteogenesis. our findings suggest that CS4-NP, an oligosaccharide-based nanomaterial, could address the limitations of current treatments and provide a viable strategy for osteoporosis.
骨质疏松症是一种以骨密度低和骨折风险增加为特征的常见疾病，给老年人带来了重大的健康挑战。目前的治疗方法虽能带来短期益处，但受长期疗效和副作用的限制，凸显了新策略的必要性。硫酸软骨素多糖（CS）是骨基质的主要成分，对骨骼和软骨健康至关重要。然而，由于天然CS的异质性，其在骨质疏松症中的作用尚未得到充分研究。我们发现骨质疏松症患者的CS水平降低，并开发了CS4-NP，一种模仿CS结构的自组装四糖纳米颗粒。CS4-NP能有效递送活性CS4，在去卵巢骨质疏松症模型中显著提高骨量。它激活前成骨细胞中的激活转录因子4-胱硫醚γ-裂解酶信号轴，增强骨生成。我们的研究结果表明，CS4-NP这种基于寡糖的纳米材料可以克服当前治疗方法的局限性，为骨质疏松症提供一种可行的策略。
