Nanoindentation modulus of murine cartilage: a sensitive indicator of the initiation and progression of post-traumatic osteoarthritis.

Nanoindentation modulus of murine cartilage: a sensitive indicator of the initiation and progression of post-traumatic osteoarthritis.
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DOI:
10.1016/j.joca.2016.08.008
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发表时间:
2017-01
影响因子:
7
通讯作者:
Han, L.
Han, L.
中科院分区:
医学2区
文献类型:
--
作者:
Doyran, B.;Tong, W.;Li, Q.;Jia, H.;Zhang, X.;Chen, C.;Enomoto-Iwamoto, M.;Lu, X. L.;Qin, L.;Han, L.

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本研究旨在证明软骨纳米压痕模量是小鼠模型中创伤后骨关节炎(PTOA)发病及时空进展的高度敏感指标。 对12周龄雄性野生型C57BL/6小鼠的右膝进行内侧半月板失稳(DMM)手术,对侧左膝作为假手术对照。在手术后3天至12周,应用基于原子力显微镜(AFM)的纳米压痕技术来量化股骨髁软骨的纳米压痕模量Eind。将模量变化与组织学骨关节炎迹象的时间线进行比较。同时,在手术后8周,评估半月板、滑膜和软骨下骨的变化以揭示PTOA的空间进展。 DMM术后1周,内侧髁软骨模量显著降低,早于组织学骨关节炎迹象,后者在术后4 - 8周才变得可检测到。这种降低可能是由于蛋白水解活性同时升高,因为在小鼠中阻断酶活性可以减弱这种模量降低。在骨关节炎后期,外侧髁软骨和内侧半月板也开始变弱,说明PTOA的全器官性质。 本研究强调了纳米压痕在检测小鼠模型中PTOA的起始、减弱和进展方面的高度敏感性。同时,模量变化突出了在骨关节炎进展过程中外侧软骨和半月板的伴随变化。
This study aims to demonstrate that cartilage nanoindentation modulus is a highly sensitive indicator of the onset and spatiotemporal progression of post-traumatic osteoarthritis (PTOA) in murine models. Destabilization of medial meniscus (DMM) surgery was performed on the right knees of 12-week old male, wild-type C57BL/6 mice, with Sham control on contralateral left knees. Atomic force microscopy (AFM)-based nanoindentation was applied to quantify the nanoindentation modulus, Eind, of femoral condyle cartilage at 3 days to 12 weeks after surgery. The modulus changes were compared against the timeline of histological OA signs. Meanwhile, at 8 weeks after surgery, changes in meniscus, synovium and subchondral bone were evaluated to reveal the spatial progression of PTOA. The modulus of medial condyle cartilage was significantly reduced at 1 week after DMM, preceding the histological OA signs, which only become detectable at 4 – 8 weeks after. This reduction is likely due to concomitantly elevated proteolytic activities, as blocking enzymatic activities in mice can attenuate this modulus reduction. In later OA, lateral condyle cartilage and medial meniscus also started to be weakened, illustrating the whole-organ nature of PTOA. This study underscores the high sensitivity of nanoindentation in examining the initiation, attenuation and progression of PTOA in murine model. Meanwhile, modulus changes highlight concomitant changes in lateral cartilage and meniscus during the advancement of OA.
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