Service of Rheumatology, Fundación Jiménez Díaz, Universidad Autónoma, Avda, Reyes Católicos, 2, 28040 Madrid, Spain.
Arthritis Res Ther. 2010;12(4):R152. doi: 10.1186/ar3103. Epub 2010 Aug 2.
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.
骨质疏松症 (OP) 会增加兔合并骨关节炎 (OA) 模型中的软骨损伤。因此，我们评估了亚髁骨微观结构损伤是否会加重该实验模型中的软骨损伤。
通过卵巢切除术和甲基强的松龙琥珀酸酯肌内注射，在 20 只雌性兔子中诱导 OP，持续四周。将 10 只健康动物作为对照。在第 7 周，所有兔子的左膝关节均接受手术诱导 OA。22 周后，处死动物，通过微计算机断层扫描评估微观结构参数，并通过 Western Blot 评估亚髁骨的护骨素 (OPG)、核因子-κB 配体受体激活剂 (RANKL)、碱性磷酸酶 (ALP) 和基质金属蛋白酶 9 (MMP9) 蛋白表达。此外，通过组织病理学 Mankin 评分评估软骨损伤。使用 SPSS 软件 v11.0 进行适当的 Mann-Whitney 和 Spearman 统计检验。当 P < 0.05 时，差异有统计学意义。
与对照组或 OA 膝关节相比，OPOA 膝关节的亚髁骨面积/组织面积、骨小梁厚度和极惯性矩减小（P < 0.05）。OA、OP 和 OPOA 膝关节的亚髁骨板厚度降低、ALP 表达和 OPG/RANKL 比值降低以及分形维数增加和 MMP9 表达增加（P < 0.05）。此外，与对照组相比，OPOA 膝关节的软骨损伤严重程度增加（P < 0.05）。值得注意的是，亚髁骨的结构和重塑参数之间以及亚髁骨结构参数与软骨 Mankin 评分之间存在良好的相关性。
与骨关节炎兔先前存在的 OP 相关的亚髁骨微观结构损伤和重塑增加加重了软骨损伤。我们的结果表明，当早期 OA 和 OP 同时存在于同一个体中时，亚髁骨吸收增加可能是软骨损伤恶化的原因。
