Investigate the Therapeutic Effect of Ibandronate Sodium on Knee Osteoarthritis Based on TLRs/MyD88/NF-κB Signaling Pathway in Vitro and in Vivo

骨关节炎 体内 医学 软骨 骨重建 药理学 体外 类风湿性关节炎 癌症研究 炎症 内科学 化学 病理 生物 生物技术 解剖 生物化学 替代医学
作者
M. X. Luo,Qingze Wang,Junguo Bao
出处
期刊:Discovery Medicine [Discovery Medicine]
卷期号:36 (180): 100-100
标识
DOI:10.24976/discov.med.202436180.9
摘要

Background: For decades, bisphosphonates have primarily found application in clinical practice for the treatment and prevention of bone metastases associated with malignant tumors and various bone metabolic disorders. However, third-generation bisphosphonates like ibandronate have demonstrated significant utility in addressing conditions like osteoporosis (OA) and other bone metabolism-related ailments. Ibandronate, distinguished by its high effectiveness, low toxicity, and ease of administration, has garnered attention for its potential applications in the treatment of rheumatoid arthritis, OA, and orthopedic concerns. In recent years, the utilization of ibandronate sodium in these contexts has sparked considerable interest. Research has pointed to a possible connection between ibandronate and the Toll-like receptors (TLRs), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) signaling pathway, particularly in the context of inflammation and immunological regulation. Consequently, this study is designed to investigate the therapeutic impact of ibandronate on in vitro and in vivo models of knee osteoarthritis, while also delving into its influence on the TLRs/MyD88/NF-κB pathway. Method: Various dosages of ibandronate sodium, including low (10 g/kg), medium (20 g/kg), and high (30 g/kg), were administered following the establishment of both in vivo and in vitro models of knee osteoarthritis (KOA). Post-intervention, an in-depth quantitative analysis of bone tissue microstructure was conducted. The morphology of articular cartilage tissue was observed in vivo, and the modified Mankin score was subsequently calculated. In the in vitro setting, cartilage was entirely isolated, and mRNA and total protein were extracted to measure the expression levels of TLR4, MyD88, and NF-κB at both the mRNA and protein levels. Furthermore, the study explored the effects of Interleukin-1 beta (IL-1β) on cell proliferation, apoptosis, stromal decomposition enzyme activity, ossification, and the expression of TLR4, MyD88, and NF-κB. Result: In the results of the in vivo experiments, several noteworthy findings emerged. The knee curvature, gait score, Mankin score, pathological knee joint injury degree, cartilage protein loss, and trabecular separation within the model group exhibited significant elevations compared to both the sham operation group and the blank control group (p < 0.05). Conversely, bone density, bone volume fraction, and trabecular thickness in the model group displayed lower values in comparison to the sham operation and blank control groups (p < 0.05). Following the administration of ibandronate sodium, there was a progressive improvement in these parameters, with the medium and high-dose groups demonstrating the most favorable outcomes (p < 0.05). Additionally, the model group exhibited the highest expression levels of TLR4, MyD88, and NF-κB, while the ibandronate sodium intervention group displayed reduced expression levels of these markers, with the high-dose group registering the most significant changes (p < 0.05). Turning to the in vitro experiments, it was observed that the cell proliferation capacity and ossification degree of the IL-1β-induced group experienced declines, concomitant with an increase in stromal decomposition enzyme activity and cell apoptosis rate (p < 0.05). However, post-intervention with ibandronate sodium, all these indicators gradually returned to normal, with the medium-dose group exhibiting the most notable improvements. The expression levels of TLR4, MyD88, and NF-κB in the IL-1β-induced group showed an increase, while the expression levels in the ibandronate sodium intervention group displayed a decrease, particularly in the high-dose group (p < 0.05). Conclusions: Ibandronate sodium demonstrates a protective effect on articular chondrocytes and exhibits the potential to decelerate the pathological progression of knee osteoarthritis (KOA) in rats. This mechanism is likely achieved through the inhibition of the TLRs/MyD88/NF-κB signaling pathway.
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