Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH, USA.
Osteoarthritis Cartilage. 2011 Apr;19(4):439-48. doi: 10.1016/j.joca.2011.01.004. Epub 2011 Jan 18.
To provide a comprehensive immunohistochemical (IHC) map of the temporal expression and tissue distribution of interleukin-1β (IL-1β) through progression of osteoarthritis (OA) in two strains of guinea pigs with varying propensity for spontaneous knee joint disease.
OA-prone Hartley and OA-resistant Strain 13 guinea pigs were collected at 60, 120, 180, 240, 360, and 480 days of age (N=4 animals per strain per date). IHC was performed on whole joint preparations; the distribution of IL-1β expression on coronal sections was mapped, semi-quantitatively scored, and correlated to OA grade using Mankin criteria with guinea pig-specific modifications. OA and IHC indices were compared among times and between strains using the Kruskal-Wallis one-way analysis of variance by ranks followed by Dunn's post test.
OA indices for both strains increased from 60 to 480 days of age; a statistically higher score (P ≤ 0.01) was found in Hartley animals at 180, 240, 360, and 480 days. At 60 days of age, IL-1β expression was detected in cartilage, menisci, synovium, and subchondral bone in both strains. Persistent and statistically increased (P<0.05) IL-1β expression was found in these same tissues in Hartley animals at 120 and 180 days, while Strain 13 animals demonstrated a significant reduction in positive immunostaining. Statistical differences in IHC indices between strains beyond 240 days of age were restricted to synovium (days 240 and 480) and subchondral bone (days 360 and 480).
As expected, histologic OA proceeded in an accelerated manner in Hartley animals relative to Strain 13 animals. The OA-prone strain did not demonstrate reduced IL-1β expression during adult maturity as occurred in the OA-resistant strain, and this persistent expression may have corresponded to early incidence of OA. Future interventional studies are warranted to explore whether dysregulation of IL-1β expression may contribute to premature onset of spontaneous disease in the Hartley guinea pig.
通过对两种易患自发性膝关节疾病的豚鼠进行研究，提供白细胞介素 1β（IL-1β）在骨关节炎（OA）进展过程中时间表达和组织分布的全面免疫组织化学（IHC）图谱。
在 60、120、180、240、360 和 480 天龄时，收集易患 OA 的 Hartley 和 OA 抗性 13 号豚鼠（每组 4 只）。对整个关节标本进行免疫组化；对冠状切片上的 IL-1β表达分布进行图谱绘制，并用 Mankin 标准进行半定量评分，并结合豚鼠特异性改良的方法与 OA 分级相关联。使用 Kruskal-Wallis 单向方差分析等级（ANOVA）对时间和菌株之间的 OA 和 IHC 指数进行比较，然后使用 Dunn 事后检验进行检验。
两种品系的 OA 指数从 60 天增加到 480 天；在 Hartley 动物中，180、240、360 和 480 天时发现统计学上更高的评分（P≤0.01）。在 60 天龄时，两种品系的软骨、半月板、滑膜和软骨下骨中均检测到 IL-1β 的表达。在 Hartley 动物中，120 和 180 天时，在这些相同组织中发现持续且统计学上增加（P<0.05）的 IL-1β 表达，而 13 号品系动物的阳性免疫染色显著减少。在 240 天龄以上，菌株之间的 IHC 指数的统计学差异仅限于滑膜（240 天和 480 天）和软骨下骨（360 天和 480 天）。
正如预期的那样，与 13 号品系动物相比，Hartley 动物的组织学 OA 以加速的方式进展。在 OA 易感性品系中，在 OA 抗性品系中发生的成年成熟时的 IL-1β 表达减少并未发生，这种持续表达可能与 OA 的早期发生相对应。未来的干预性研究是必要的，以探索 IL-1β 表达的失调是否可能导致 Hartley 豚鼠自发性疾病的早期发生。
