Runx2、Dkk-1和PTH1R在大鼠膝骨关节炎模型软骨中的表达及意义

Expression and their Significance of Runx2,Dkk-1 and PTH1R in the Cartilage in Rat Model of Knee Osteoarthritis

目的观察大鼠膝骨关节炎模型软骨中Runt相关转录因子2(Runx2)、Dickkopf-1(Dkk-1)和甲状旁腺激素受体1(PTH1R)的表达,探讨其在膝骨关节炎发生发展中的作用。方法将32只10周龄雄性SD大鼠,随机分为假手术组(n=16)和膝骨关节炎模型组(n=16)。模型组行前交叉韧带切断及部分内侧半月板切除术,分别于造模2周和6周后取右膝关节股骨内侧髁软骨,根据改良Mankin评分对HE染色膝关节软骨进行病理观察及评分。免疫组织化学染色检测Runx2、Dkk-1和PTH1R在各组膝关节软骨中的表达水平。结果模型组与同时段假手术组比较、模型组6周与模型组2周比较均显示膝关节软骨明显退变,Mankin评分及Runx2和Dkk-1的阳性细胞率均明显增高,PTH1R阳性细胞率明显降低(P均<0.05)。结论在膝骨关节炎软骨中,Runx2、Dkk-1的高表达和PTH1R的低表达,可能促进下游信号因子释放,导致软骨细胞肥大和软骨细胞外基质分解,促进软骨退变。

Objective To observe the expression of Runt-related transcription factor 2( Runx2),Dkk-1and Parathyroid hormone receptor( PTH1R) in the cartilage in rat model of knee osteoarthritis and to explore their significance in the development of osteoarthritis. Methods A total of 32 male Sprague-Dawley rats,10 weeks old,were randomly divided into two groups: sham group( n = 16) and knee osteoarthritis model group( n = 16). In the model group,rats received the anterior cruciate ligament transection in combination with partial medial meniscectomy( ACLT + MMx) and materials were taken at 2 and 6 weeks respectively. The histopathological features of cartilage with Hematoxylin / Eosin staining were evaluated by a modified scoring system by Mankin. Immunohistochemical staining was used to analyze the expression of Runx2,Dkk-1 and PTH1 R in the cartilage. Results At the same time,index in the model group compared to that in the sham group,index in the ACLT + MMx group at 6 weeks compared to that in the ACLT + MMx group at 2 weeks,articular cartilage degeneration significantly increased and the modified Mankin score and expression of Runx2,Dkk-1 significantly increased in the cartilage while expression of PTH1 R significantly decreased( P <0. 05). Between sham-operated group at 2 weeks and sham-operated group at 6 weeks,there were no significant differences in articular cartilage degeneration,the Mankin scores and expression of Runx2,Dkk-1and PTH1 R in the cartilage( P > 0. 05). Conclusion In the cartilage in rat model of knee osteoarthritis,the expression of Runx2 and Dkk-1 were significantly increased,while PTH1 R was significantly decreased,which may promote the release of downstream signaling factors,lead to chondrocytes hypertrophy and cartilage matrix degeneration,thereby increasing degeneration of cartilage.