骨关节炎关节软骨中衰老相关β-半乳糖苷酶和c-Fos蛋白的表达及意义
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摘要
目的:
研究SA-beta-gal、c-Fos蛋白在正常关节软骨和骨关节炎不同退变程度关节软骨中表达水平的差异,探讨SA-beta-gal、c-Fos蛋白与OA软骨退变程度的相关性及其在骨关节炎发病过程中的可能作用,为进一步明确骨关节炎的发病机制提供线索。
方法:
选取正常关节软骨标本10个,骨关节炎软骨标本26个,根据大体观察凿取正常和OA不同退变严重程度软骨块50个,再根据关节软骨改良Mankin病理评分法进行分组,正常关节软骨标本9个(A组),OA软骨轻度退变标本10个(B组),OA软骨中度退变标本15个(C组),OA软骨重度退变标本13个(D组)(有3个标本因脱片或取材失误予以排除)。采用免疫组化SABC法,计算各组标本中软骨细胞SA-beta-gal、c-Fos蛋白染色阳性细胞率,比较各组中二者阳性细胞率的差异性并分析其与关节软骨不同退变程度之间的相关性。结果:
1.A组无SA-beta-gal染色阳性软骨细胞,B组SA-beta-gal染色阳性细胞率为13.00±5.77%,C组SA-beta-gal染色阳性细胞率为31.65±6.91%,D组SA-beta-gal染色阳性细胞率为51.95±6.21%,各组之间SA-beta-gal染色阳性细胞率差异具有显著性(P＜0.05)。
2.A组c-Fos蛋白染色阳性细胞率为1.08±1.39%,B组c-Fos蛋白染色阳性细胞率为25.76±8.81%,C组c-Fos蛋白染色阳性细胞率为36.70±4.22%,D组c-Fos蛋白染色阳性细胞率为12.37±8.85%,各组之间c-Fos蛋白染色阳性细胞率差异具有显著性(P＜0.05)。在软骨细胞增多、紊乱、细胞成簇的区域c-Fos蛋白表达增多。
3.软骨中SA-beta-gal阳性细胞率与改良Mankin病理评分呈正相关(r=0.940,p＜0.05),c-Fos蛋白阳性细胞率与改良Mankin病理评分无明显相关性(r=0.275,P＞0.05),SA-beta-gal阳性细胞率与c-Fos蛋白阳性细胞率无明显相关性(r=0.164,P＞0.05)。
结论:
1.软骨细胞衰老是OA可能的发病机理之一。
2.随着衰老软骨细胞阳性率逐渐增加,软骨退变程度逐渐加重,软骨细胞衰老与OA病程进展有关。
3.c-Fos蛋白与OA软骨退变严重程度和软骨细胞衰老均无直接相关性,但可能在软骨退变早中期促进软骨细胞代偿性分裂增殖活跃。
Objective: To study the expression of senescence-associated beta-galactosidase(SA-beta-gal) and c-Fos protein in the different impaired cartilage of osteoarthritis(OA).To approach the correlation and possible involvement of senescent chondrocyte and c-fos oncogene in pathogenesis and progression of human osteoarthritis .
Methods: To collect 50 cartilage specimens from OA and normal joint, on the basis of improved Mankin pathological score to divide into four groups , normal group 9 specimens(group A), mild impaired group 10 specimens(group B), medium impaired group 15 specimens(group C), severe impaired group 13 specimens(group D)(3 specimens discarded because of experimental mistake). Then use the immunohistochemistry to detect the expression of SA-beta-gal and c-Fos protein in the cartilage specimens. To calculate the percentage of the positive chondrocytes and analysis the correlation between the percentage of the positive chondrocytes and the different impaired cartilage.
Results:
1.There are no SA-beta-gal positive chondrocytes in the group A , the percentage of the SA-beta-gal positive chondrocytes in the group B is 13.00±5.77%,the percentage of the SA-beta-gal positive chondrocytes in the group C is 31.65±6.91%, the percentage of the SA-beta-gal positive chondrocytes in the group D is 51.95±6.21%,there are significant differences between each group (p<0.05) .
2. The percentage of the c-Fos protein positive chondrocytes in the group A is 1.08±1.39%, the percentage of the c-Fos protein positive chondrocytes in the group B is 25.76±8.81%, the percentage of the c-Fos protein positive chondrocytes in the group C is 36.70±4.22%, the percentage of the c-Fos protein positive chondrocytes in the group D is 12.37±8.85%, there are significant differences between each group(p<0.05) .
3. According to Spearman rank correlation test, the percentage of the SA-beta-gal positive chondrocytes have direct correlation with the improved Mankin pathological score (r=0.940, p<0.05). The percentage of the c-Fos positive chondrocytes have no correlation with the improved Mankin pathological score (r=0.275, P>0.05) . The percentage of the c-Fos positive chondrocytes have no correlation with the percentage of the SA-beta-gal positive chondrocytes (r=0.164, P >0.05) .
Conclusion:
1.The senescence of chondrocytes maybe is one of important pathogenesis in OA.
2.With the cartalege of OA impaired by degrees, the percentage of the senescent chondrocytes increases.
3.The expression of c-Fos protein shows no direct correlation with the severity of OA and the percentage of the SA-beta-gal positive chondrocytes,but increases in the mild and medium impaired cartilage, indicate that c-fos oncogene may play an important role in the early and medium stage OA to compensate for cell division.
研究SA-beta-gal、c-Fos蛋白在正常关节软骨和骨关节炎不同退变程度关节软骨中表达水平的差异,探讨SA-beta-gal、c-Fos蛋白与OA软骨退变程度的相关性及其在骨关节炎发病过程中的可能作用,为进一步明确骨关节炎的发病机制提供线索。
方法:
选取正常关节软骨标本10个,骨关节炎软骨标本26个,根据大体观察凿取正常和OA不同退变严重程度软骨块50个,再根据关节软骨改良Mankin病理评分法进行分组,正常关节软骨标本9个(A组),OA软骨轻度退变标本10个(B组),OA软骨中度退变标本15个(C组),OA软骨重度退变标本13个(D组)(有3个标本因脱片或取材失误予以排除)。采用免疫组化SABC法,计算各组标本中软骨细胞SA-beta-gal、c-Fos蛋白染色阳性细胞率,比较各组中二者阳性细胞率的差异性并分析其与关节软骨不同退变程度之间的相关性。结果:
1.A组无SA-beta-gal染色阳性软骨细胞,B组SA-beta-gal染色阳性细胞率为13.00±5.77%,C组SA-beta-gal染色阳性细胞率为31.65±6.91%,D组SA-beta-gal染色阳性细胞率为51.95±6.21%,各组之间SA-beta-gal染色阳性细胞率差异具有显著性(P＜0.05)。
2.A组c-Fos蛋白染色阳性细胞率为1.08±1.39%,B组c-Fos蛋白染色阳性细胞率为25.76±8.81%,C组c-Fos蛋白染色阳性细胞率为36.70±4.22%,D组c-Fos蛋白染色阳性细胞率为12.37±8.85%,各组之间c-Fos蛋白染色阳性细胞率差异具有显著性(P＜0.05)。在软骨细胞增多、紊乱、细胞成簇的区域c-Fos蛋白表达增多。
3.软骨中SA-beta-gal阳性细胞率与改良Mankin病理评分呈正相关(r=0.940,p＜0.05),c-Fos蛋白阳性细胞率与改良Mankin病理评分无明显相关性(r=0.275,P＞0.05),SA-beta-gal阳性细胞率与c-Fos蛋白阳性细胞率无明显相关性(r=0.164,P＞0.05)。
结论:
1.软骨细胞衰老是OA可能的发病机理之一。
2.随着衰老软骨细胞阳性率逐渐增加,软骨退变程度逐渐加重,软骨细胞衰老与OA病程进展有关。
3.c-Fos蛋白与OA软骨退变严重程度和软骨细胞衰老均无直接相关性,但可能在软骨退变早中期促进软骨细胞代偿性分裂增殖活跃。
Objective: To study the expression of senescence-associated beta-galactosidase(SA-beta-gal) and c-Fos protein in the different impaired cartilage of osteoarthritis(OA).To approach the correlation and possible involvement of senescent chondrocyte and c-fos oncogene in pathogenesis and progression of human osteoarthritis .
Methods: To collect 50 cartilage specimens from OA and normal joint, on the basis of improved Mankin pathological score to divide into four groups , normal group 9 specimens(group A), mild impaired group 10 specimens(group B), medium impaired group 15 specimens(group C), severe impaired group 13 specimens(group D)(3 specimens discarded because of experimental mistake). Then use the immunohistochemistry to detect the expression of SA-beta-gal and c-Fos protein in the cartilage specimens. To calculate the percentage of the positive chondrocytes and analysis the correlation between the percentage of the positive chondrocytes and the different impaired cartilage.
Results:
1.There are no SA-beta-gal positive chondrocytes in the group A , the percentage of the SA-beta-gal positive chondrocytes in the group B is 13.00±5.77%,the percentage of the SA-beta-gal positive chondrocytes in the group C is 31.65±6.91%, the percentage of the SA-beta-gal positive chondrocytes in the group D is 51.95±6.21%,there are significant differences between each group (p<0.05) .
2. The percentage of the c-Fos protein positive chondrocytes in the group A is 1.08±1.39%, the percentage of the c-Fos protein positive chondrocytes in the group B is 25.76±8.81%, the percentage of the c-Fos protein positive chondrocytes in the group C is 36.70±4.22%, the percentage of the c-Fos protein positive chondrocytes in the group D is 12.37±8.85%, there are significant differences between each group(p<0.05) .
3. According to Spearman rank correlation test, the percentage of the SA-beta-gal positive chondrocytes have direct correlation with the improved Mankin pathological score (r=0.940, p<0.05). The percentage of the c-Fos positive chondrocytes have no correlation with the improved Mankin pathological score (r=0.275, P>0.05) . The percentage of the c-Fos positive chondrocytes have no correlation with the percentage of the SA-beta-gal positive chondrocytes (r=0.164, P >0.05) .
Conclusion:
1.The senescence of chondrocytes maybe is one of important pathogenesis in OA.
2.With the cartalege of OA impaired by degrees, the percentage of the senescent chondrocytes increases.
3.The expression of c-Fos protein shows no direct correlation with the severity of OA and the percentage of the SA-beta-gal positive chondrocytes,but increases in the mild and medium impaired cartilage, indicate that c-fos oncogene may play an important role in the early and medium stage OA to compensate for cell division.
引文
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[2]Brandt K D,Block J A,Michalski J P,Moreland L W,Caldwell J R,Lavin PT,O RTHOVISC Study Group.Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis.Clinical Orthopaedics and Related Research.2001,1(385):130-143
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