Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis.
Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis.
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DOI：
10.1186/ar3103
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发表时间：
2010
影响因子：
4.9
通讯作者：
Herrero-Beaumont G
中科院分区：
文献类型：
--
作者：
Bellido M;Lugo L;Roman-Blas JA;Castañeda S;Caeiro JR;Dapia S;Calvo E;Largo R;Herrero-Beaumont G
骨质疏松症（OP）在骨性关节炎（OA）联合兔模型中增加软骨损伤。因此，我们在该实验模型中评估软骨下骨微结构损伤是否会加重软骨损伤。采用切除卵巢并肌内注射半半月甲强的松龙4周的方法，对20只雌性家兔进行OP诱导。10只健康动物作为对照。第7周，所有家兔左膝均行手术诱导骨关节炎。22周时，采用显微计算机断层扫描评估软骨下骨组织微结构参数，Western Blot检测软骨下骨组织骨保护素（OPG）、核因子-κB配体受体激活物（RANKL）、碱性磷酸酶（ALP）和金属蛋白酶9 （MMP9）蛋白表达。此外，使用组织病理学Mankin评分评估软骨损伤。采用SPSS v 11.0软件进行Mann-Whitney和Spearman统计检验。P < 0.05，差异有统计学意义。软骨下骨面积/组织面积、骨小梁厚度、极惯性矩均明显低于对照组（P < 0.05）。与对照组相比，OA、OP和OPOA膝关节软骨下骨的板厚、ALP表达和OPG/RANKL比值降低，分形维数和MMP9表达增加（P < 0.05）。此外，与对照组相比，OPOA组膝关节软骨损伤严重程度增加（P < 0.05）。值得注意的是，软骨下骨的结构参数和重构参数之间以及软骨下结构参数与软骨Mankin评分之间存在良好的相关性。软骨下骨微结构损伤与既往OP的骨性关节炎家兔软骨损伤重建增加相关。我们的研究结果表明，当同一个体同时存在早期OA和OP时，软骨下骨吸收增加可能是软骨损伤加剧的原因。
Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model. OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabbits. At 22 weeks, after sacrifice, microstructure parameters were assessed by micro-computed tomography, and osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), alkaline phosphatase (ALP) and metalloproteinase 9 (MMP9) protein expressions were evaluated by Western Blot at subchondral bone. In addition, cartilage damage was estimated using the histopathological Mankin score. Mann-Whitney and Spearman statistical tests were performed as appropriate, using SPSS software v 11.0. Significant difference was established at P < 0.05. Subchondral bone area/tissue area, trabecular thickness and polar moment of inertia were diminished in OPOA knees compared with control or OA knees (P < 0.05). A decrease of plate thickness, ALP expression and OPG/RANKL ratio as well as an increased fractal dimension and MMP9 expression occurred at subchondral bone of OA, OP and OPOA knees vs. controls (P < 0.05). In addition, the severity of cartilage damage was increased in OPOA knees vs. controls (P < 0.05). Remarkably, good correlations were observed between structural and remodelling parameters at subchondral bone, and furthermore, between subchondral structural parameters and cartilage Mankin score. Microstructure impairment at subchondral bone associated with an increased remodelling aggravated cartilage damage in OA rabbits with previous OP. Our results suggest that an increased subchondral bone resorption may account for the exacerbation of cartilage damage when early OA and OP coexist simultaneously in same individuals.
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影响因子：
--
作者：
Kadri, A.;Ea, H. K.;Cohen-Solal, M. E.
通讯作者：
Cohen-Solal, M. E.
影响因子：
7
作者：
Cake, MA;Appleyard, RC;Ghosh, P
通讯作者：
Ghosh, P
影响因子：
7
作者：
Calvo, E;Palacios, I;Herrero-Beaumont, G
通讯作者：
Herrero-Beaumont, G
影响因子：
4.1
作者：
Bobinac, D;Spanjol, J;Maric, I
通讯作者：
Maric, I
影响因子：
1.8
作者：
Boyd, SK;Müller, R;Zernicke, RF
通讯作者：
Zernicke, RF