Loeser Richard F, Olex Amy L, McNulty Margaret A, Carlson Cathy S, Callahan Michael F, Ferguson Cristin M, Chou Jeff, Leng Xiaoyan, Fetrow Jacquelyn S
Molecular Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Arthritis Rheum. 2012 Mar;64(3):705-17. doi: 10.1002/art.33388.
To better understand the contribution of age to the development of osteoarthritis (OA).
Surgical destabilization of the medial meniscus (DMM) was used to model OA in 12-week-old and 12-month-old male C57BL/6 mice. OA severity was evaluated histologically. RNA used for microarray and real-time polymerase chain reaction analysis was isolated from joint tissue collected from the medial side of the joint, including cartilage, meniscus, subchondral bone, and the joint capsule with synovium. Computational analysis was used to identify patterns of gene expression, and immunohistochemistry was used to evaluate tissue distribution of selected proteins.
OA was more severe in older mice than in young mice. Only 55 genes showed a similar expression with DMM-induced OA in the 2 age groups, while 493 genes showed differential expression, the majority having increased expression in older mice. Functional categories for similarly expressed genes included extracellular matrix- and cell adhesion-related genes; differentially expressed genes included those related to muscle structure and development and immune response genes. Comparison of expression in sham-operated control joints revealed an age-related decrease in matrix gene expression and an increase in immune and defense response gene expression. Interleukin-33 was present in multiple joint tissue cells, while CCL21 was more localized to chondrocytes and meniscal cells. Periostin was found in the extracellular matrix of cartilage and meniscus.
Age affects both the basal pattern of gene expression in joint tissues and the response to surgically induced OA. Examining tissue from the joint beyond only cartilage revealed novel genes and proteins that would be important to consider in OA.
为了更好地理解年龄对骨关节炎（OA）发展的影响。
采用内侧半月板手术失稳（DMM）法在12周龄和12月龄雄性C57BL/6小鼠中建立OA模型。通过组织学评估OA严重程度。用于微阵列和实时聚合酶链反应分析的RNA取自关节内侧收集的关节组织，包括软骨、半月板、软骨下骨以及带有滑膜的关节囊。采用计算分析来识别基因表达模式，并使用免疫组织化学评估所选蛋白质的组织分布。
老年小鼠的OA比年轻小鼠更严重。在两个年龄组中，只有55个基因在DMM诱导的OA中表现出相似的表达，而493个基因表现出差异表达，其中大多数在老年小鼠中表达增加。相似表达基因的功能类别包括细胞外基质和细胞黏附相关基因；差异表达基因包括与肌肉结构和发育以及免疫反应基因相关的基因。对假手术对照关节中表达的比较显示，基质基因表达存在与年龄相关的下降，免疫和防御反应基因表达增加。白细胞介素-33存在于多个关节组织细胞中，而CCL21更多地定位于软骨细胞和半月板细胞。骨膜蛋白在软骨和半月板的细胞外基质中被发现。
年龄既影响关节组织中基因表达的基础模式，也影响对手术诱导的OA的反应。检查关节中不仅是软骨的组织发现了对OA研究很重要的新基因和蛋白质。
