Department of Joint Surgery and Sports Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Department of Applied Mechanics and Biomedical Engineering, Indian Institute of Technology-Madras, Chennai - 600 036, Tamil Nadu, India; Department of Prosthodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600 077, Tamil Nadu, India.
Int J Biol Macromol. 2024 Aug;274(Pt 2):133492. doi: 10.1016/j.ijbiomac.2024.133492. Epub 2024 Jun 27.
Anti-osteoporotic agents are clinically employed to improve bone health and prevent osteoporotic fractures. In the current study, we investigated the potential of chitosan-quercetin bio-conjugate as an anti-osteoporotic agent. The conjugate was prepared and characterized by FTIR and found notable interactions between chitosan and quercetin. Treating mouse MSCs with the bioconjugate in osteogenic conditions for a week led to elevated expression of differentiation markers Runx2, ALP, and Col-I, as determined by real-time PCR analysis. Evaluation at the cellular level using alizarin red staining demonstrated enhanced calcium deposition in MSCs following treatment with the bioconjugate. Likewise, ELISA analysis showed significantly elevated levels of secretory osteocalcin and osteonectin in groups treated with the conjugate. To broaden our comprehension, we utilized a zebrafish-based in vivo model of dexamethasone-induced osteoporosis to investigate bone regeneration. Toxicity profiling with zebrafish larvae confirmed the bio-conjugate's compatibility at a concentration of 25 μg/ml, underscoring the significance of finding the right dosage. Furthermore, in zebrafish models of osteoporosis, the bio-conjugate demonstrated significant potential for bone regeneration, as indicated by improved bone calcification, callus formation, and overall bone healing in a tail fin fracture model. Additionally, the study revealed that the bio-conjugate inhibited osteoclastic activity, leading to reduced TRAP activity and hydroxyproline release, suggesting its effectiveness in mitigating bone resorption. In conclusion, our research provides compelling evidence for the osteogenic capabilities of the chitosan-quercetin bio-conjugate, highlighting its promising applications in regenerative medicine and the treatment of conditions like osteoporosis.
抗骨质疏松药物临床上用于改善骨骼健康和预防骨质疏松性骨折。在本研究中，我们研究了壳聚糖-槲皮素生物缀合物作为抗骨质疏松药物的潜力。通过傅里叶变换红外光谱（FTIR）对缀合物进行了制备和表征，发现壳聚糖和槲皮素之间存在显著的相互作用。在成骨条件下，用生物缀合物处理小鼠间充质干细胞（MSCs）一周，通过实时 PCR 分析发现分化标志物 Runx2、ALP 和 Col-I 的表达水平升高。用茜素红染色在细胞水平上进行评估表明，用生物缀合物处理后 MSCs 中的钙沉积增加。同样，ELISA 分析显示，用缀合物处理的组中分泌型骨钙素和骨粘连蛋白的水平显著升高。为了拓宽我们的理解，我们利用基于斑马鱼的地塞米松诱导骨质疏松症的体内模型研究骨再生。用斑马鱼幼虫进行毒性分析证实，在 25μg/ml 的浓度下，生物缀合物具有兼容性，这突显了找到合适剂量的重要性。此外，在骨质疏松症的斑马鱼模型中，生物缀合物表现出显著的骨再生潜力，表现为尾巴骨折模型中骨钙化、骨痂形成和整体骨愈合的改善。此外，该研究表明，生物缀合物抑制破骨细胞活性，导致 TRAP 活性和羟脯氨酸释放减少，表明其在减轻骨吸收方面的有效性。总之，我们的研究为壳聚糖-槲皮素生物缀合物的成骨能力提供了有力的证据，突出了其在再生医学和骨质疏松症等疾病治疗中的应用前景。
