ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes
ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes
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DOI：
10.1016/j.joca.2008.09.018
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发表时间：
2009-05-01
影响因子：
7
通讯作者：
van Osch, G. J. V. M.
中科院分区：
文献类型：
--
作者：
Botter, S. M.;Glasson, S. S.;van Osch, G. J. V. M.
目的：骨关节炎（OA）以关节软骨损伤和软骨下骨改变为特征。先前的研究表明，聚集酶-2缺陷（ADAMTS5-/-）小鼠可以免受关节不稳定引起的软骨损伤。本研究分析了这种对软骨的保护作用是否也反映在软骨下骨结构中。方法：取10周龄雄性野生型（WT）和ADAMTS5-/-小鼠右膝关节，横断内侧半月板胫韧带诱导OA，左膝关节不做手术。8周后进行膝关节微ct扫描。选择胫骨近端进行进一步分析。组织学观察软骨损伤和破骨细胞的存在。结果：与WT关节相比，ADAMTS5-/-关节软骨下板明显变薄，骨骺小梁骨明显减少。组织学证实了先前的发现，在不稳定诱导的OA模型中，ADAMTS5-/-小鼠的软骨损伤明显小于WT。尽管在两种基因型的手术关节中，胫骨内侧平台处的软骨下骨板明显变厚，但ADAMTS5-/-小鼠的百分比增加明显较小（WT: 20.7 +/- 4.7%, ADAMTS5-/-: 8.3 +/- 1.2%）。在ADAMTS5-/-动物中，Oc.N均显著降低。/BS和Oc.S./BS。最后，在WT而不是ADAMTS5-/-小鼠中，发现内侧软骨下板厚度与胫骨内侧平台软骨损伤之间存在显著相关性。结论：与WT小鼠相比，未受软骨损伤保护的ADAMTS5-/-关节的软骨下骨结构发生了轻微变化，而WT小鼠的软骨下骨结构发生了明显变化。这一发现表明，在不稳定诱导的OA中，软骨损伤过程和软骨下骨变化之间存在联系。(C) 2008国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: Osteoarthritis (OA) is characterized by damaged articular cartilage and changes in subchondral bone. Previous work demonstrated aggrecanase-2 deficient (ADAMTS5-/-) mice to be protected from cartilage damage induced by joint instability. This study analyzed whether this protective effect on cartilage is also reflected in the subchondral bone structure.Methods: Right knee joints from 10-week old male wild type (WT) and ADAMTS5-/- mice received transection of the medial meniscotibial ligament to induce OA, whereas left knees were left unoperated. After 8 weeks knee joints were scanned by micro-CT. The proximal tibia was selected for further analysis. Histology was performed to evaluate cartilage damage and osteoclast presence.Results: ADAMTS5-/- joints had a significantly thinner subchondral plate and less epiphyseal trabecular bone compared to WT joints. Histology confirmed previous findings that ADAMTS5-/- mice have significantly less cartilage damage than WT in the instability-induced OA model. Although the subchondral bone plate became significantly thicker at the medial tibial plateau in operated joints of both genotypes, the percentage increase was significantly smaller in ADAMTS5-/- mice (WT: 20.7 +/- 4.7%, ADAMTS5-/-: 8.3 +/- 1.2% compared to the left unoperated control joint). In ADAMTS5-/- animals a significant decrease was found in both Oc.N./BS and Oc.S./BS. Finally, in WT but not in ADAMTS5-/- mice a significant correlation was found between medial subchondral bone plate thickness and cartilage damage at the medial tibial plateau.Conclusion: ADAMTS5-/- joints that were protected from cartilage damage showed minor changes in the subchondral bone structure, in contrast to WT mice where substantial changes were found. This finding suggests links between the process of cartilage damage and subchondral bone changes in instability-induced OA. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.