Analysis of early biochemical markers and regulation by tin protoporphyrin IX in a model of spontaneous osteoarthritis

Analysis of early biochemical markers and regulation by tin protoporphyrin IX in a model of spontaneous osteoarthritis
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DOI:
10.1016/j.exger.2012.03.005
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发表时间:
2012-05-01
影响因子:
3.9
通讯作者:
Jose Alcaraz, Maria
Jose Alcaraz, Maria
中科院分区:
医学2区
文献类型:
--
作者:
Braza-Boils, Aitana;Luisa Ferrandiz, Maria;Jose Alcaraz, Maria

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关节组织中的骨关节炎相关变化导致骨关节炎(OA)。发现OA患者的早期变化可能有助于在不可逆的关节破坏建立之前开始治疗。STR/ort小鼠随着年龄的增长发展为类似于人类OA的严重退行性关节疾病,从而允许在加速的时间范围内研究生化标志物以及新的治疗方法。我们分析了STR/ort小鼠特发性OA早期血清中不同介质水平的变化。血清基质金属蛋白酶-3(MMP-3)水平与9周时STR/ort小鼠膝关节的组织病理学变化相关,而肿瘤坏死因子-α、白细胞介素(IL)-1 β、IL-17或前列腺素E-2水平与之无关。用锡原卟啉IX(SnPP,12 mg/kg/天i. p.)持续4周显著降低了OA的进展。我们的数据表明,MMP-3是一个敏感的生物标志物,以检测早期OA的变化和SnPP可能是一种保护剂在OA。(C)2012 Elsevier Inc. All rights reserved.
Age-related changes in joint tissues lead to osteoarthritis (OA). Detection of early changes in OA patients may help to initiate treatments before the establishment of irreversible joint destruction. STR/ort mice develop with age a severe degenerative joint disease that resembles human OA thus allowing the investigation of biochemical markers as well as new treatments in an accelerated time frame. We have analyzed the changes in serum levels of different mediators during the early phases of idiopathic OA in STR/ort mice. Serum levels of matrix metalloproteinase-3 (MMP-3) but not those of tumor necrosis factor-alpha, interleukin(IL)-1 beta, IL-17 or prostaglandin E-2 correlated with histopathological changes in knees of STR/ort mice at 9 weeks. Treatment of animals with tin protoporphyrin IX (SnPP, 12 mg/kg/day i.p.) for 4 weeks significantly reduced the progression of OA. Our data suggest that MMP-3 is a sensitive biomarker to detect early OA alterations and that SnPP could be a protective agent in OA. (C) 2012 Elsevier Inc. All rights reserved.