Brama P A J, van den Boom R, DeGroott J, Kiers G H, van Weeren P R
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht, The Netherlands.
Equine Vet J. 2004 Jan;36(1):34-40. doi: 10.2746/0425164044864705.
Matrix metalloproteinases (MMPs) are considered candidate biomarkers for both physiological and pathological tissue remodelling because of their key role in articular cartilage homeostasis. As disruption of the collagenous architecture is thought to be pivotal in chronic degenerative diseases such as osteoarthritis (OA), the collagenases form an interesting subset of the MMPs. The significance of any biomarker in synovial fluid (SF) can be assessed properly only when fluctuations in patterns induced by physiological processes such as development and growth, and by external influences and interventions such as exercise and repeated arthrocentesis, are known and taken into account.
To investigate the activity of MMP-1 in equine SF at different stages of development and in joints affected by OA, and the influence of exercise and repeated arthrocentesis thereon.
MMP-1 activity was determined in SF of normal joints of fetal, juvenile and mature horses, and in SF of horses suffering from OA, using an internally quenched fluorogenic peptide substrate. MMP-1 activity was also measured in SF from horses subjected to an exercise regimen and those subjected to repeated arthrocentesis.
An age-related decline in the SF levels of active MMP-1 was observed. MMP-1 activity was 15-fold higher in fetal than in juvenile animals, which showed significantly higher MMP-1 activity levels than mature horses. In SF of OA joints, MMP-1 activity was increased. Exercise did not affect MMP-1 activity in SF, but repeated arthrocentesis (within 60 h) increased MMP-1 activity significantly.
The high MMP-1 activity in SF of young individuals parallels the high metabolic activity occurring during rapid growth and differentiation at early age. The elevated MMP-1 activity in SF of OA joints probably reflects pathological matrix degradation, confirming the potential of MMP-1 to serve as a biochemical marker for early joint disease. Moderate exercise is not likely to influence the outcome of MMP-1 activity measurements in equine SF, but arthrocentesis should be taken into account as a possible confounding factor.
Given the crucial role of the collagen matrix for tissue integrity, MMP-1 activity may be a useful tool in diagnostic, therapeutic or prognostic studies in horses suspected of OA. However, care should be taken to exclude fluctuations in MMP-1 activity induced by physiological processes such as development and growth, and by interventions such as repeated arthrocentesis.
基质金属蛋白酶（MMPs）因其在关节软骨稳态中的关键作用，被视为生理和病理组织重塑的候选生物标志物。由于胶原结构的破坏被认为在骨关节炎（OA）等慢性退行性疾病中起关键作用，胶原酶构成了MMPs中一个有趣的亚组。只有当已知并考虑到由发育和生长等生理过程以及运动和反复关节穿刺等外部影响和干预引起的模式波动时，才能正确评估滑膜液（SF）中任何生物标志物的意义。
研究不同发育阶段和患OA关节的马的滑膜液中MMP-1的活性，以及运动和反复关节穿刺对其的影响。
使用内部淬灭的荧光肽底物，测定胎儿、幼年和成年马正常关节滑膜液以及患OA马的滑膜液中MMP-1的活性。还测定了接受运动方案的马和接受反复关节穿刺的马的滑膜液中MMP-1的活性。
观察到活性MMP-1的滑膜液水平随年龄下降。胎儿的MMP-1活性比幼年动物高15倍，幼年动物的MMP-1活性水平显著高于成年马。在OA关节的滑膜液中，MMP-1活性增加。运动不影响滑膜液中MMP-1的活性，但反复关节穿刺（60小时内）显著增加MMP-1活性。
年轻个体滑膜液中高MMP-1活性与幼年快速生长和分化期间发生的高代谢活性平行。OA关节滑膜液中升高的MMP-1活性可能反映了病理性基质降解，证实了MMP-1作为早期关节疾病生化标志物的潜力。适度运动不太可能影响马滑膜液中MMP-1活性的测量结果，但关节穿刺应被视为一个可能的混杂因素。
鉴于胶原基质对组织完整性的关键作用，MMP-1活性可能是怀疑患OA的马的诊断、治疗或预后研究中的有用工具。然而，应注意排除由发育和生长等生理过程以及反复关节穿刺等干预引起的MMP-1活性波动。
