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首页> 外文期刊>BMC Musculoskeletal Disorders >Effects of pamidronate disodium on the loss of osteoarthritic subchondral bone and the expression of cartilaginous and subchondral osteoprotegerin and RANKL in rabbits
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Effects of pamidronate disodium on the loss of osteoarthritic subchondral bone and the expression of cartilaginous and subchondral osteoprotegerin and RANKL in rabbits

机译：帕米膦酸二钠对兔骨关节炎软骨下骨丢失及软骨和软骨下骨保护素和RANKL表达的影响

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Background Osteoarthritis (OA) is a major health problem in the increasingly elderly population. Therefore, it is crucial to prevent and treat OA at an early stage. The present study investigated whether pamidronate disodium (PAM), a bone-loss inhibitor, can significantly prevent or reverse the progression of early anterior cruciate ligament transection (ACLT)-induced OA. Whether therapeutic intervention is associated with regulation of the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or subchondral bone was also investigated. Methods 60 New Zealand rabbits were randomized into four groups: Sham-operated (n = 20); ACLT (n = 20); short-term treatment with PAM (PAM-S, n = 10) and long-term treatment with PAM (PAM-L, n = 10). For cartilage and subchondral bone testing, rabbits from Sham and ACLT groups were harvested at 2, 4, 6, and 14?weeks. Rabbits were given PAM from the 4th week after ACLT operation in PAM-S and PAM-L group, and were harvested at 6 and 14?weeks, respectively. Trabecular characteristics and cartilage changes were detected using Micro-CT, safranin O and rapid green staining, respectively. Immunohistochemical staining for OPG and RANKL were also performed. OPG, RANKL, MMP-9 and TLR-4 expression was evaluated by western blot analysis. Results Micro-CT and histology analyses indicated that PAM treatment for 2 or 10?weeks could completely prevent or reverse osteoarthritic subchondral bone loss and cartilage surface erosion. Immunohistochemistry and western blot analysis indicated that expression of OPG and RANKL increased, although RANKL expression increased more significantly than that of OPG. Therefore the ratio of OPG to RANKL was lower in the ACLT group. However, the ratio of OPG to RANKL in the PAM group was significantly higher than that in the ACLT group. Additionally, expression of MMP-9 and TLR-4 were upregulated in the ACLT group and downregulated in the PAM treated groups. Conclusions PAM can significantly inhibit and even reverse early osteoarthritic subchondral bone loss, thus alleviating the process of cartilaginous degeneration. The mechanisms involved may be associated with the upregulation of OPG expression, and downregulation of RANKL, MMP-9 and TLR-4 expression.
机译：背景技术骨关节炎（OA）是日益增长的老年人口中的主要健康问题。因此，早期预防和治疗OA至关重要。本研究调查了骨丢失抑制剂帕米膦酸二钠（PAM）是否可以显着预防或逆转早期十字交叉韧带横断（ACLT）诱导的OA的进展。治疗干预是否与软骨中骨保护素（OPG），核因子-κB配体的受体激活剂（RANKL），金属蛋白酶9（MMP-9）或Toll样受体4（TLR-4）的表达调控有关。还研究了软骨下和/或软骨下骨。方法60只新西兰大白兔随机分为四组：假手术组（n = 20）;假手术组（n = 20）。 ACLT（n = 20）; PAM的短期治疗（PAM-S，n = 10）和PAM的长期治疗（PAM-L，n = 10）。为了进行软骨和软骨下骨测试，在第2、4、6和14周时从Sham和ACLT组中收获兔子。 PAM-S组和PAM-L组在ACLT手术后第4周开始给予兔PAM，分别在第6周和第14周收获。分别使用Micro-CT，番红花O和快速绿色染色检测小梁特征和软骨变化。还进行了OPG和RANKL的免疫组织化学染色。通过蛋白质印迹分析评估OPG，RANKL，MMP-9和TLR-4的表达。结果显微CT和组织学分析表明PAM治疗2或10周可以完全预防或逆转骨关节炎软骨下骨丢失和软骨表面侵蚀。免疫组织化学和蛋白质印迹分析表明OPG和RANKL的表达增加，尽管RANKL的表达比OPG的增加更显着。因此，在ACLT组中OPG与RANKL的比率较低。但是，PAM组中OPG与RANKL的比率显着高于ACLT组。另外，ACLT组中MMP-9和TLR-4的表达上调，而PAM治疗组中MMP-9和TLR-4的表达下调。结论PAM可以显着抑制甚至逆转早期的骨关节炎软骨下骨丢失，从而减轻软骨变性的过程。涉及的机制可能与OPG表达的上调，RANKL，MMP-9和TLR-4表达的下调有关。

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