Li Chen-Guang, Liang Qian-Qian, Zhou Quan, Menga Emmanuel, Cui Xue-Jun, Shu Bing, Zhou Chong-Jian, Shi Qi, Wang Yong-Jun
Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Spine (Phila Pa 1976). 2009 Jun 1;34(13):1363-9. doi: 10.1097/BRS.0b013e3181a3c7c7.
Pathologic changes were observed in the spine of small mother against decapentaplegic (Smad) 3 mice at different time points.
To observe the degeneration of the intervertebral disc (IVD) in Smad3 gene knock-out mice with growth.
Smad3 gene knock-out (Smad3) mice displays phenotypes similar to human osteoarthritis. Despite the similarities between IVD cartilage endplate and the articular cartilage, there has been relatively little interest in exploring the possibility that IVD degeneration might be driven by the deficiency of Smad3.
The Smad3 mice were killed at the 10th, 30th, and 60th day after their birth and the IVD samples of spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples were used for real-time PCR analysis of type II collagen (Col2alpha1), type X collagen (Col10alpha1), aggrecan, and transforming growth factor-beta1 (TGF-beta1).
Compared with the wild-type mice, Smad3 mice appeared significantly smaller in size. Radiograph showed that the spine of Smad3 mice is malformation and kyphosis. Histologic analysis revealed the declined height of cartilage endplate, decreased proteoglycan and collagen content in disc of Smad3 mice. With growth, especially of the 30- and 60-day old Smad3 mice, the protein positive staining of type II collagen, aggrecan, and TGF-beta1 in the disc decreased, while that of type X collagen increased. And the analysis of real-time PCR showed that the mRNA expression of Col2alpha1, aggrecan, and TGF-beta1 decreased, while that of Col10alpha1 increased.
Smad3 gene knock-out mice develop IVD degeneration with growth.
在不同时间点观察小母亲抗五肢瘫（Smad）3小鼠脊柱的病理变化。
观察Smad3基因敲除小鼠椎间盘（IVD）随生长的退变情况。
Smad3基因敲除（Smad3）小鼠表现出与人类骨关节炎相似的表型。尽管IVD软骨终板与关节软骨存在相似性，但对于探索IVD退变可能由Smad3缺乏引起的可能性的关注相对较少。
在出生后第10天、30天和60天处死Smad3小鼠，采集脊柱的IVD样本进行组织学和免疫组织化学研究。从这些样本中分离的总RNA用于对II型胶原（Col2alpha1）、X型胶原（Col10alpha1）、聚集蛋白聚糖和转化生长因子-β1（TGF-β1）进行实时PCR分析。
与野生型小鼠相比，Smad3小鼠体型明显更小。X线片显示Smad3小鼠脊柱畸形和驼背。组织学分析显示Smad3小鼠软骨终板高度降低，椎间盘蛋白聚糖和胶原含量减少。随着生长，尤其是30日龄和60日龄的Smad3小鼠，椎间盘中II型胶原、聚集蛋白聚糖和TGF-β1的蛋白阳性染色减少，而X型胶原的阳性染色增加。实时PCR分析显示Col2alpha1、聚集蛋白聚糖和TGF-β1的mRNA表达降低，而Col10alpha1的表达增加。
Smad3基因敲除小鼠随生长出现IVD退变。
