Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career.

Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career.
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DOI:
10.1186/s12917-016-0873-7
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发表时间:
2016-11-08
影响因子:
2.6
通讯作者:
Brkljaca-Bottegaro N
Brkljaca-Bottegaro N
中科院分区:
农林科学2区
文献类型:
--
作者:
Bertuglia A;Pagliara E;Grego E;Ricci A;Brkljaca-Bottegaro N

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关节撞击伤可引起进行性关节损伤,最终导致创伤后骨关节炎(PTOA)。赛马代表了一种理想的、自然可用的疾病动物模型。我们的研究对象是职业生涯第一年患创伤性胎儿关节骨性关节炎的标准种马。同时纳入年龄匹配的对照组。马骨性关节炎的生物标志物水平在基线时测量血清和滑液(SF),并在接下来的4年训练(从T1到T4)中每年重复一次。分析了时间和疾病对生物标志物浓度的影响,并评估了它们与临床和放射学参数的关系。我们假设,关节疾病的促炎细胞因子和结构生物标志物的动力学将显示创伤后骨关节炎期间关节退行性变的进展,并阐明早期关节创伤的影响。PTOA组SF中IL-1、IL-6、肿瘤坏死因子-α的浓度在T0时达到峰值,T1时下降,然后随时间递增,从T3开始高于基线水平。PTOA马和对照马的CTXII和COMP水平在基线时相似,从T2(血清和滑膜CTXII)和血清COMP(血清COMP)或T3(滑膜COMP)开始,PTOA马的血清和滑液中CTXII和COMP水平升高。肿瘤坏死因子-α在受累关节SF中的百分比变化独立地解释了T3端与T2端和T4端与T3端的放射学变化。创伤性胎儿性骨关节炎急性发作时部分生物标志物的时间变化表明,SF和血清中炎性细胞因子、II型胶原碎片和COMP的长期浓度增加与PTOA有关。根据观察到的T1时炎性信号分子的减少,我们假设PTOA的进展可以通过适当的治疗策略得到有效的调节。滑膜中肿瘤坏死因子-α浓度的年变化可以可靠地预测其放射学进展。
Joint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disease on the biomarker concentrations were analysed, and their relationship with clinical and radiographic parameters were assessed. We hypothesized that the kinetics of pro-inflammatory cytokines and structural biomarkers of joint disease would demonstrate progression of degenerative joint status during post-traumatic osteoarthritis and clarify the effect of early joint trauma. The concentrations of IL1-ß, IL-6, TNF-α in the SF of PTOA group peaked at T0, decreased at T1, and then progressively increased with time, reaching levels higher than those observed at baseline starting from T3. CTXII and COMP levels were similar in PTOA and control horses at baseline, and increased in serum and synovial fluid of PTOA horses starting from T2 (serum and synovial CTXII, and serum COMP) or T3 (synovial COMP). The percentual change of TNF-α in the SF of the affected joints independently contributed to explaining the radiological changes at T3 vs T2 and T4 vs T3. Temporal changes of selected biomarkers in STBRs with an acute episode of traumatic fetlock OA demonstrated that long-term increased concentrations of inflammatory cytokines, type II collagen fragments and COMP, in the SF and serum, are related to PTOA. Based on the observed decrease in inflammatory merkers at T1, we hypothesize that the progression of PTOA could be effectively modulated by proper treatment strategies. Annual variations of synovial concentration of TNF-α can reliably predict radiographic progression of PTOA.
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