Therapeutic effect of targeting Substance P on the progression of osteoarthritis
Therapeutic effect of targeting Substance P on the progression of osteoarthritis
复制标题
靶向P物质对骨关节炎进展的治疗作用
DOI：
10.1093/mr/roab089
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发表时间：
2021
期刊：
影响因子：
2.2
通讯作者：
Adachi N.
中科院分区：
文献类型：
--
作者：
Shirakawa Y;Nakasa T;Kanemitsu M;Nekomoto A;Ishikawa M;Yimiti D;Miyaki S;Adachi N.
目的P物质（Substance P，SP）通过调节NK1而发挥疼痛、骨代谢和血管生成等多种作用，是骨关节炎（Osteoarthritis，OA）发病的重要因素。我们的目的是评估的治疗效果，有针对性的SP对OA progress.MethodsSP的表达模式进行了组织学分析，在关节软骨和软骨下骨的人膝关节OA患者和尸检供体作为非OA样本，并在小鼠关节软骨。此外，为了检查SP对OA进展的影响，我们在内侧半月板手术去稳定后向小鼠施用药物：PBS、Septide（NK1受体激动剂）或阿瑞匹坦（NK1受体拮抗剂）。组织学分析和骨形态学分析，使用microCT performed.ResultsIn人类分析，SP的表达在轻度OA样品中显着高于严重OA，在健康软骨显着高于OA。在小鼠分析中，Septide组的OARSI评分显著低于对照组。CT分析显示，在对照组的软骨下骨的骨骺硬化的变化不存在于septide group.ConclusionsThe管理septide通过防止软骨下骨硬化改善OA进展。
ObjectivesSubstance P (SP) modulates NK1 and has various functions such as pain, bone metabolism and angiogenesis, which are recognized as important factors in the osteoarthritis (OA). We aimed to evaluate the therapeutic effect of targeting SP on OA progression.MethodsSP expression patterns were analyzed histologically in articular cartilage and subchondral bone of human knees from OA patients and autopsy donors as non-OA samples, and in mice articular cartilage. Moreover, to examine the effect of SP on the progression of OA, we administered drugs to mice following surgical destabilization of the medial meniscus: PBS, septide (NK1 receptor agonist), or aprepitant (NK1 receptor antagonist). Histological analysis and bone morphologic analysis using microCT was performed.ResultsIn human analysis, the expression of SP in mild OA samples was significantly higher than that in severe OA, and that in healthy cartilage was significantly higher than that in OA. In mouse analysis, OARSI scores in the septide group were significantly lower than that in the control group. CT analysis showed that the subchondral bone's epiphysis in the control group had sclerotic change not present in the septide group.ConclusionsThe administration of septide ameliorates OA progression through preventing subchondral bone sclerosis.