Elevated expression of ICAM‐1 in synovium is associated with early inflammatory response for cartilage degeneration in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is increasingly being recognized as an independent risk factor for the onset and progression of osteoarthritis (OA). Extensive studies have focused on the contribution of obesity (excessive mechanical stress), comorbidity frequently found in T2DM, to cartilage destruction during OA development. However, a little is known about how diabetes‐related inflammation may affect the local cartilage in a diabetic objective. In the present study, we were able to establish a T2DM rat model using a combination of a low dose of streptozotocin with high‐fat and high‐sugar diet. Although the cartilage integrity was comparable between the control and T2DM groups, the expression of matrix metalloproteinases‐13 (MMP‐13) was significantly upregulated in T2DM, indicating the initiation of an early cascade of cartilage degeneration. In parallel, an obvious alteration of subchondral bone remodeling (inhibition of bone formation) was observed, as evidenced by the reduction of osterix‐expressing positive cells. Moreover, we demonstrated that the expression of intercellular adhesion molecule‐1 (ICAM‐1) in the serum and synovium of T2DM rats was elevated, accompanied by an increase of synovitis score. We also noticed that the number of F4/80‐positive macrophage cells was significantly increased in the T2DM group. Mechanistically, the expression of ICAM‐1 in fibroblast‐like synoviocytes can be triggered by glucose and interleukin‐1β, which are the two important factors within the joint of T2DM. Given that MMP‐13 expression was significantly upregulated in the T2DM cartilage, and that ICAM‐1‐mediated filtration of macrophage was associated with synovitis, we propose that ICAM‐1 is essential for triggering a vicious cycle of inflammation within the joint, which together subsequently drivers the cartilage degradation. Streptozotocin‐ and dietary‐induced type 2 diabetes mellitus (T2DM) inhibits bone formation during subchondral bone remodeling T2DM model exhibits an increase of intercellular adhesion molecule‐1 (ICAM‐1) expression in both serum and synovium ICAM‐1 is a hallmark of diabetes‐related inflammation that drives the initiation of early cartilage destruction in T2DM.