Microarray analysis reveals age‐related differences in gene expression during the development of osteoarthritis in mice

Abstract

Objective To better understand the contribution of age to the development of osteoarthritis (OA). Methods Surgical destabilization of the medial meniscus (DMM) was used to model OA in 12 week-old and 12 month-old male C57/BL6 mice. OA severity was evaluated histologically. RNA used for microarrays and real-time PCR was isolated from joint tissue collected from the medial side of the joint, including cartilage, meniscus, subchondral bone, and joint capsule with synovium. Computational analysis was used to identify patterns of gene expression and immunohistochemistry to evaluate tissue distribution of selected proteins. Results OA was more severe in older mice than young. Only 55 genes showed a similar expression with DMM-induced OA in the two 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 muscle structure and development and immunoglobulin domain genes. Comparison of expression in the sham control joints revealed an age-related decrease in matrix gene expression and an increase in immune and defense response genes. IL-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. Conclusion 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.

Time‐series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis

“…Although the lack of any solely age-related decline in muscle-specific gene expression in those studies may be due to their inclusion of non-AC tissues (43), their findings support a role for a muscle signature in OA. The role of this program clearly requires further interrogation.…”

Expression of p16INK4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

“…The DMM surgery (Glasson, Blanchet & Morris, 2007) was performed on mice at 12 months of age as described previously (Loeser et al., 2012). Briefly, mice were anesthetized with isoflurane, access to the joint space was obtained through a para‐patellar incision, and the medial meniscotibial ligament was transected using a scalpel.…”

Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis

“…Although interpretation of in vivo experiments may not be straightforward and mouse models may not mimic all aspects of human disease, they do allow us to study the time course of the disease in a way that is not possible in humans Little and Fosang, 2010]. Gene profiling in experimental OA models has provided additional targets for consideration [Appleton et al 2007;Bernardo et al 2011;Lodewyckx et al 2012;Loeser et al 2012;Yasuhara et al 2011]. Furthermore, certain mediators that determine initiation and progression of cartilage damage are common to all of these models.…”