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通过手术诱导关节不稳定来诱发骨关节炎后,ADAMTS5基因敲除小鼠的软骨下骨变化较少:这对软骨与软骨下骨变化之间的联系具有启示意义。

ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes.

作者信息

Botter S M, Glasson S S, Hopkins B, Clockaerts S, Weinans H, van Leeuwen J P T M, van Osch G J V M

机构信息

Erasmus MC, University Medical Center Rotterdam, Department of Orthopedics, The Netherlands.

出版信息

Osteoarthritis Cartilage. 2009 May;17(5):636-45. doi: 10.1016/j.joca.2008.09.018. Epub 2008 Oct 17.

Abstract

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.

摘要

目的

骨关节炎(OA)的特征是关节软骨受损和软骨下骨改变。先前的研究表明,缺乏聚集蛋白聚糖酶-2(ADAMTS5-/-)的小鼠可免受关节不稳定诱导的软骨损伤。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

对10周龄雄性野生型(WT)和ADAMTS5-/-小鼠的右膝关节进行内侧半月板胫骨韧带横断以诱导OA,而左膝不进行手术。8周后,通过微型计算机断层扫描(micro-CT)对膝关节进行扫描。选择胫骨近端进行进一步分析。进行组织学检查以评估软骨损伤和破骨细胞的存在。

结果

与WT关节相比,ADAMTS5-/-关节的软骨下板明显更薄,骨骺小梁骨更少。组织学证实了先前的发现,即在不稳定诱导的OA模型中,ADAMTS5-/-小鼠的软骨损伤明显少于WT小鼠。尽管在两种基因型的手术关节中,胫骨内侧平台的软骨下骨板明显增厚,但ADAMTS5-/-小鼠的增厚百分比明显较小(与左侧未手术对照关节相比,WT:20.7±4.7%,ADAMTS5-/-:8.3±1.2%)。在ADAMTS5-/-动物中,发现骨表面破骨细胞数(Oc.N./BS)和骨表面破骨细胞表面积(Oc.S./BS)均显著降低。最后,在WT小鼠而非ADAMTS5-/-小鼠中,发现胫骨内侧平台软骨下骨板厚度与软骨损伤之间存在显著相关性。

结论

与发现有显著变化的WT小鼠相比,免受软骨损伤的ADAMTS5-/-关节的软骨下骨结构仅有微小变化。这一发现表明,在不稳定诱导的OA中,软骨损伤过程与软骨下骨变化之间存在联系。

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