Growth and repair factors, osteoactivin, matrix metalloproteinase and heat shock protein 72, increase with resolution of inflammation in musculotendinous tissues in a rat model of repetitive grasping.
Growth and repair factors, osteoactivin, matrix metalloproteinase and heat shock protein 72, increase with resolution of inflammation in musculotendinous tissues in a rat model of repetitive grasping.
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DOI：
10.1186/s12891-016-0892-3
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发表时间：
2016-01-18
影响因子：
2.3
通讯作者：
Barbe MF
中科院分区：
文献类型：
--
作者：
Frara N;Abdelmagid SM;Tytell M;Amin M;Popoff SN;Safadi FF;Barbe MF
在组织退行性变和再生、骨折修复和失神经导致的废用性萎缩过程中，生长因子骨激活素(OA)的表达增加，同时伴随着基质金属蛋白酶(MMPs)的增加。然而，OA在反复过度使用损伤中的表达尚不清楚。本研究的目的是评估：1)反复过度使用的可操作性大鼠模型中OA的表达；2)MMPs的表达；3)指示损伤或炎症的炎性细胞因子；以及4)热休克蛋白70的诱导形式(HSPA1A/HSP72)，因为后者已知在代谢应激期间增加并参与细胞修复。年轻的成年雌性大鼠进行高重复可忽略力(HRNF)食物提取任务长达6周，并与对照组大鼠进行比较。取青年成年雌性大鼠22只，完成3~6周的高分辨神经营养因子到达任务，另取12只限食对照(FRC)大鼠。定量聚合酶链式反应(QPCR)检测OAm RNA水平。用Western blotting检测OA、MMP1、-2、-3、-13和HSP72蛋白的表达。免疫组织化学和图像分析技术检测骨性关节炎和热休克蛋白72的表达。采用ELISA法检测HSP72和炎性细胞因子。与FRC大鼠相比，6周龄HRNF大鼠的屈指肌肉和肌腱显示出更高的OAmRNA和蛋白表达。肌内基质金属蛋白酶-1、-2和-3呈进行性增加，肌腱中基质金属蛋白酶-1和-3呈递增趋势。与对照组相比，HSP72在6周的HRNF肌肉和肌腱中增加，并与OA共同定位于肌纤维肌膜。肌腱或肌肉中IL-1α和β在HRNF第3周出现一过性升高，到第6周才消失。OA与组织修复相关因子(MMPs和HSP72)的同时升高支持了OA在重复过度使用后的组织再生中的作用。
Expression of the growth factor osteoactivin (OA) increases during tissue degeneration and regeneration, fracture repair and after denervation-induced disuse atrophy, concomitant with increased matrix metalloproteinases (MMPs). However, OA’s expression with repetitive overuse injuries is unknown. The aim of this study was to evaluate: 1) OA expression in an operant rat model of repetitive overuse; 2) expression of MMPs; 3) inflammatory cytokines indicative of injury or inflammation; and 4) the inducible form of heat shock protein 70 (HSPA1A/HSP72) as the latter is known to increase during metabolic stress and to be involved in cellular repair. Young adult female rats performed a high repetition negligible force (HRNF) food retrieval task for up to 6 weeks and were compared to control rats. Flexor digitorum muscles and tendons were collected from 22 young adult female rats performing a HRNF reaching task for 3 to 6 weeks, and 12 food restricted control (FRC) rats. OA mRNA levels were assessed by quantitative polymerase chain reaction (qPCR). OA, MMP-1, -2, -3, and -13 and HSP72 protein expression was assayed using Western blotting. Immunohistochemistry and image analysis was used to evaluate OA and HSP72 expression. ELISA was performed for HSP72 and inflammatory cytokines. Flexor digitorum muscles and tendons from 6-week HRNF rats showed increased OA mRNA and protein expression compared to FRC rats. MMP-1, -2 and -3 progressively increased in muscles whereas MMP-1 and -3 increased in tendons with HRNF task performance. HSP72 increased in 6-week HRNF muscles and tendons, compared to controls, and co-localized with OA in the myofiber sarcolemma. IL-1alpha and beta increased transiently in tendons or muscles in HRNF week 3 before resolving in week 6. The simultaneous increases of OA with factors involved in tissue repair (MMPs and HSP72) supports a role of OA in tissue regeneration after repetitive overuse.