Samman Waad A, Mosalam Esraa M, Saif Dalia S, Abdallah Mahmoud S, Zidan Abdel-Aziz A, Sallam Amany Said, Abdelsattar Shimaa, Khalil Fatma Omar, Elashkar Amany E, Mohamed Somia Mokabel, Al-Ghannam Mohamed, Abo Mansour Hend E
Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Saudi Arabia.
Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
Front Pharmacol. 2025 Feb 25;16:1507693. doi: 10.3389/fphar.2025.1507693. eCollection 2025.
Understanding the molecular mechanism underlying the pathogenesis of knee osteoarthritis (KOA) may be beneficial in fetching new therapeutics. Our study aims to investigate the implication of Wnt/ β-catenin pathway in development of KOA by detection of the downstream target genes and their crosstalk with miR-214 in patients with KOA and to correlate that with the clinical findings.
Sixty participants were involved in the study. The levels of miR-214, β-catenin, Wnt4, matrix metalloproteinase 3 (MMP3), Bax, caspase 3, and phosphorylated glycogen synthase kinase-3 beta (pGSK3β) were determined. All participants were assessed clinically and radiologically regarding knee joint pain, stiffness, range of motion, and knee medial cartilage thickness. Besides, a correlation between Western Ontario and McMaster Universities (WOMAC) score, clinical, and radiological data, and the measured parameters was conducted.
Patients with KOA showed downregulated miR-214 with upregulated β-catenin, Wnt4, MMP3, Bax, caspase 3, and pGSK3β compared to healthy individuals. Statistically significant positive correlation between WOMAC score, knee joint pain regarding Visual Analogue Scale (VAS) with β-catenin, pGSK3β, Wnt4, MMP3, Bax, and caspase 3, and significant negative relationship between them and knee joint medial cartilage thickness; while there was a statistically significant negative correlation between WOMAC, and clinical findings of osteoarthritis and miR-214 and significant positive relationship between it and knee joint medial cartilage thickness. This study provides valuable insights into involvement of the Wnt/β-catenin and miR-214 in KOA pathogenesis. By targeting these molecular components, future therapeutics may modulate their activity and mitigate chondrocyte apoptosis and matrix degradation, potentially halting KOA progression.
了解膝骨关节炎（KOA）发病机制的分子机制可能有助于开发新的治疗方法。我们的研究旨在通过检测KOA患者下游靶基因及其与miR-214的相互作用，研究Wnt/β-连环蛋白通路在KOA发病中的作用，并将其与临床结果相关联。
60名参与者参与了该研究。测定了miR-214、β-连环蛋白、Wnt4、基质金属蛋白酶3（MMP3）、Bax、半胱天冬酶3和磷酸化糖原合酶激酶-3β（pGSK3β）的水平。所有参与者均就膝关节疼痛、僵硬、活动范围和膝关节内侧软骨厚度进行了临床和放射学评估。此外，还对西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分、临床和放射学数据与测量参数之间的相关性进行了分析。
与健康个体相比，KOA患者的miR-214表达下调，β-连环蛋白、Wnt4、MMP3、Bax、半胱天冬酶3和pGSK3β表达上调。WOMAC评分、视觉模拟量表（VAS）评估的膝关节疼痛与β-连环蛋白、pGSK3β、Wnt4、MMP3、Bax和半胱天冬酶3之间存在统计学显著正相关，与膝关节内侧软骨厚度之间存在显著负相关；而WOMAC与骨关节炎的临床结果和miR-214之间存在统计学显著负相关，与膝关节内侧软骨厚度之间存在显著正相关。本研究为Wnt/β-连环蛋白和miR-214参与KOA发病机制提供了有价值的见解。通过靶向这些分子成分，未来的治疗方法可能调节它们的活性，减轻软骨细胞凋亡和基质降解，从而可能阻止KOA的进展。
