van den Boom R, van der Harst M R, Brommer H, Brama P A J, Barneveld A, van Weeren P R, DeGroot J
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Equine Vet J. 2005 Jan;37(1):19-25. doi: 10.2746/0425164054406919.
Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting horses and leads to degeneration of articular cartilage. Diagnosis is based on clinical signs in combination with radiography, which is relatively insensitive and provides only an indication of accumulated damage. Alternative methods, such as molecular markers, are therefore needed that can quantitatively, reliably and sensitively detect osteoarthritic changes in the joints at an early stage of the disease. If such markers are to be used reliably, it is important to know the relationship between marker concentration and cartilage composition.
To study the relationship between cartilage composition, synovial fluid levels of glycosaminoglycans (GAGs), hydroxyproline (Hyp) and general matrix metalloproteinase (MMP) activity, and the presence and severity of articular cartilage damage on the articular surface of P1.
Synovial fluid (SF) was collected from the metacarpophalangeal joints of 60 mature horses, and levels of GAGs, Hyp and general MMP activity were determined. Further, GAG and denatured collagen content of the articular cartilage were determined at the dorsal articular margin of P1 (site 1) and central cavity (site 2). The presence and severity of cartilage change was quantified using the cartilage degeneration index (CDI), measured at the same 2 sites. Correlations between SF parameters, cartilage composition and degree of cartilage degeneration were sought using correlation analysis.
There was no correlation between GAG or Hyp content of SF and the amount of GAGs or denatured collagen, respectively, in cartilage. In joints with moderate to severe cartilage damage, the GAG content of site 1 was significantly lower than in joints with no to minimal cartilage change (P = 0.005) and there was a negative correlation between the amount of denatured collagen and GAG content at site 1 in all joints (r = -039, P = 0.002). Further, in joints with moderate to severe cartilage damage, there was a significant positive correlation between MMP activity in SF and Hyp levels in SF (r = 0.72, P < 0.001) and CDI at sites 1 (r = 0.46, P = 0.03) and 2 (r = 0.43, P = 0.04).
General MMP activity in joints with moderate to severe cartilage damage is related to the severity of those cartilage changes and to Hyp levels in SF. Glycosaminoglycan levels in SF are not directly related to MMP activity, GAG content of articular cartilage or severity of cartilage change.
Glycosaminoglycan levels in SF are not helpful for the early detection of cartilage lesions. In damaged joints, Hyp levels may give an indication of the severity of cartilage change as they are strongly related to MMP activity, but do not qualify as markers for the presence or absence of cartilage lesions.
骨关节炎(OA)是影响马匹的最常见且致残的慢性疾病之一,会导致关节软骨退变。诊断基于临床症状并结合X线摄影,而X线摄影相对不敏感,只能显示累积损伤情况。因此,需要诸如分子标志物等替代方法,能够在疾病早期阶段定量、可靠且灵敏地检测关节中的骨关节炎变化。若要可靠地使用此类标志物,了解标志物浓度与软骨成分之间的关系很重要。
研究P1关节表面软骨成分、滑液中糖胺聚糖(GAGs)、羟脯氨酸(Hyp)水平及一般基质金属蛋白酶(MMP)活性与关节软骨损伤的存在及严重程度之间的关系。
从60匹成年马的掌指关节采集滑液,测定GAGs、Hyp水平及一般MMP活性。此外,在P1的背侧关节边缘(部位1)和中央腔(部位2)测定关节软骨的GAG和变性胶原含量。使用软骨退变指数(CDI)对软骨变化的存在及严重程度进行量化,在相同的2个部位进行测量。通过相关性分析寻找滑液参数、软骨成分与软骨退变程度之间的相关性。
滑液中GAG或Hyp含量与软骨中GAGs或变性胶原含量之间无相关性。在中度至重度软骨损伤的关节中,部位1的GAG含量显著低于无至轻度软骨变化的关节(P = 0.005),且在所有关节中,部位1的变性胶原量与GAG含量之间呈负相关(r = -0.39,P = 0.002)。此外,在中度至重度软骨损伤的关节中,滑液中MMP活性与滑液中Hyp水平之间存在显著正相关(r = 0.72,P < 0.001),与部位1(r = 0.46,P = 0.03)和部位2(r = 0.43,P = 0.04)的CDI也存在显著正相关。
中度至重度软骨损伤关节中的一般MMP活性与这些软骨变化的严重程度及滑液中Hyp水平有关。滑液中糖胺聚糖水平与MMP活性、关节软骨GAG含量或软骨变化严重程度无直接关系。
滑液中糖胺聚糖水平无助于早期检测软骨损伤。在受损关节中,Hyp水平可能因与MMP活性密切相关而提示软骨变化的严重程度,但不能作为软骨损伤存在与否的标志物。