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创伤性骨关节炎术后小鼠模型中的肌肉功能障碍。

Impaired muscle function in a mouse surgical model of post-traumatic osteoarthritis.

机构信息

Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Australia.

Institute of Sport, Exercise & Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia.

出版信息

Osteoarthritis Cartilage. 2016 Jun;24(6):1047-53. doi: 10.1016/j.joca.2015.12.008. Epub 2015 Dec 31.

DOI:10.1016/j.joca.2015.12.008
PMID:26746150
Abstract

OBJECTIVES

Using a mouse surgical model of post-traumatic osteoarthritis (OA), we sought to determine if muscle function is altered following acute joint injury and whether this relates to OA progression.

DESIGN

Male C57BL/6 mice underwent surgical transection of the medio-meniscal tibial ligament destabilisation of the medial meniscus (DMM) or sham surgery on one knee. Tibialis anterior (TA) muscle function was assessed in situ at 1, 4 and 8 weeks post-surgery. Cartilage damage and joint inflammation were assessed by histologic scoring. Muscle mRNA expression was quantified by qRT-PCR.

RESULTS

Tetanic and twitch force production between DMM and sham muscle did not differ at 1 week post-surgery. Muscle function improved in both groups with time, but specific force production in DMM muscles was 18% and 22% lower than sham muscles at 4 and 8 weeks post-surgery respectively. At 8 weeks post-surgery, DMM muscles had a 40% slower relaxation rate and reduced expression of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (Serca) pump mRNA compared to sham muscles; both observations indicate likely alterations in muscle Ca(2+) handling. There were no histologic signs of muscle atrophy or inflammation in DMM TA muscles. Specific force production in both sham and DMM mice showed a negative correlation with the severity of joint inflammation.

CONCLUSIONS

Acute knee injury in the DMM model of post-traumatic OA leads to a persistent deficit in TA muscle function that occurs in the absence of muscle atrophy. This study highlights that the impact of acute knee injury is unlikely to be limited to the muscles controlling knee movement.

摘要

目的

利用小鼠创伤性骨关节炎(OA)的外科模型,我们试图确定急性关节损伤后肌肉功能是否发生改变,以及这种改变是否与 OA 的进展有关。

设计

雄性 C57BL/6 小鼠一侧膝关节接受内侧半月板中-内侧胫骨韧带切断术(DMM)或假手术。术后 1、4 和 8 周,在体评估胫骨前肌(TA)的肌肉功能。通过组织学评分评估软骨损伤和关节炎症。通过 qRT-PCR 定量肌肉 mRNA 表达。

结果

DMM 和假手术肌肉的强直和颤搐力在术后 1 周时没有差异。两组肌肉功能随时间改善,但 DMM 肌肉的比力在术后 4 和 8 周时分别比假手术肌肉低 18%和 22%。术后 8 周,DMM 肌肉的松弛速率比假手术肌肉慢 40%,肌浆/内质网 Ca2+ATP 酶(Serca)泵 mRNA 表达减少;这两种观察结果都表明肌肉 Ca2+处理可能发生改变。DMM TA 肌肉中没有肌肉萎缩或炎症的组织学迹象。假手术和 DMM 小鼠的比力与关节炎症的严重程度呈负相关。

结论

DMM 型创伤后 OA 模型中的急性膝关节损伤导致 TA 肌肉功能持续缺陷,而没有肌肉萎缩。本研究表明,急性膝关节损伤的影响不太可能仅限于控制膝关节运动的肌肉。

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