The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice.
The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice.
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DOI：
10.1016/j.bone.2011.03.773
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发表时间：
2011-06-01
期刊：
影响因子：
4.1
通讯作者：
Wang, Yong-Jun
中科院分区：
文献类型：
--
作者：
Liang, Qian-Qian;Li, Xiao-Feng;Zhou, Quan;Xing, Lianping;Cheng, Shao-Dan;Ding, Dao-Fang;Xu, Le-Qin;Tang, De-Zhi;Bian, Qin;Xi, Zhi-Jie;Zhou, Chongjian;Shi, Qi;Wang, Yong-Jun
人软骨细胞和椎间盘纤维环细胞表达骨保护素(OPG)，但OPG在IVD退变发病机制中的作用尚不清楚。在这里，我们评估了骨质疏松症−/−小鼠的血管性痴呆的表型变化。对12、20、28周龄−/−小鼠和WT对照组的IVD进行组织学分析，包括破骨细胞的TRAP染色、OPG和I型胶原蛋白的免疫染色以及细胞凋亡的TUNEL染色。实时定量RT-PCR检测成骨细胞--Osterix、ALP和Osteocalin，破骨细胞--TRAP、RANK、MMP9和组织蛋白酶K，软骨细胞--aggrecan、MMP13和Col10基因的表达。WT小鼠IVDS的终板软骨和纤维环细胞表达OPG蛋白。与WT小鼠相比，OPG−/−小鼠出现了与衰老相关的软骨丢失和终板上的骨组织出现。从20周龄开始，OPG−/−小鼠IVD的MMP13和COL10水平显著增加，这与成骨细胞数量增加和成骨细胞标志基因表达增加有关。OPG−/−小鼠终板软骨内可见TRAP+破骨细胞。这些破骨细胞位于软骨附近，侵蚀软骨。在OPG−/−IVD中RANK、MMP9和Cathepsin k的表达增加。IVD中的OPG通过防止破骨细胞介导的终板软骨吸收，在终板软骨老化过程中起着重要的作用。
Human chondrocytes and annulus fibrosus cells of intervertebral disc (IVD) express osteoprotegerin (OPG), but the effect of OPG on the pathogenesis of IVD degeneration remains unknown. Here we assessed the phenotype change of IVD in OPG−/− mice. The IVDs from 12-, 20-, and 28-week-old OPG−/− mice and WT controls were subjected to histologic analyses including TRAP staining for osteoclasts, immunostaining for OPG and type I collagen protein expression, and TUNEL staining for apoptosis. The IVD tissues were also subjected to real time RT-PCR for mRNA expression of genes for osteoblast-osterix, ALP, and osteocalcin; for osteoclasts-trap, rank, mmp9 and cathepsin K, and for chondrocytes-aggrecan, mmp13 and Col10. OPG protein expresses at the cells of endplate cartilage and annulus fiborsis in IVDs of WT mice. Compared to WT mice, OPG−/− mice developed aging related cartilage loss and bony tissue appearance at the endplate. Stating from 20 weeks of age, IVDs from OPG−/− mice expressed significantly increased mmp13 and Col10 levels, which is associated with increased osteoblast number and elevated expression of osteoblast marker genes. Furthermore, TRAP+ osteoclasts were presented in the endplate cartilage of OPG−/− mice. These osteoclasts localized adjacently to and erosion into the cartilage. Increased expression of RANK, mmp9 and cathepsin k was detected in OPG−/− IVDs. OPG at IVD plays an important role for maintaining the integrity of endplate cartilage during aging by preventing endplate cartilage from osteoclast-mediated resorption.
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影响因子：
4.8
作者：
Nakamura, M;Udagawa, N;Takahashi, N
通讯作者：
Takahashi, N
影响因子：
3
作者：
Urban, JPG;Smith, S;Fairbank, JCT
通讯作者：
Fairbank, JCT
影响因子：
64.8
作者：
WANG, ZQ;OVITT, C;WAGNER, EF
通讯作者：
WAGNER, EF
影响因子：
1.8
作者：
Spahni, Andrea I.;Schawalder, Peter;Stoffel, Michael H.
通讯作者：
Stoffel, Michael H.
影响因子：
5.5
作者：
Tat, Steeve Kwan;Amiable, Nathalie;Martel-Pelletier, Johanne
通讯作者：
Martel-Pelletier, Johanne