Diabetes Promotes Mild Osteoarthritis in The Streptozotocin‐ Induced Diabetic Mouse Model

Abstract

Osteoarthritis (OA) is a degenerative joint disease that affects millions of people worldwide. In the United States alone OA affects more than 30 million adults. Several risk factors for OA are well studied, still, there are no therapies to prevent OA. Diabetes mellitus has emerged as a possible risk factor for OA. However, the current literature shows inconsistent results and most of these studies do not address the molecular changes associated with this effect. In addition, most of these studies do not account for changes in body mass index, a well-known risk factor for OA. In the present study, we first aimed to determine if diabetes is indeed a risk factor for OA, independently of body mass index. Next, we examined diabetes-related molecular changes in the mouse cartilage knee joints that could contribute to OA. We hypothesized that diabetes would promote OA. Sixteen weeks old streptozotocin-induced diabetic male mice were assessed for OA and molecular changes in the knee cartilage joint. Cartilage degeneration measurements of the knee joint show a mild OA phenotype in the diabetic group, characterized by proteoglycan loss, when compared to the control group, suggesting that diabetes can moderately promote OA. However, diabetes does not intensify post-traumatic osteoarthritis induced by a non-invasive tibial compression injury model. Changes in cartilage knee joint gene expression by RNA sequencing (RNAseq) identified 519 up regulated genes and 645 down regulated genes differentially regulated between diabetic and non-diabetic animals. This includes known regulators of cartilage and bone remodeling genes such as Col11a2, Col27a1, Mmp28, Adam33, Bglap, Ctsk and Acp5. Our findings suggest that diabetes can be a risk factor for OA, and we identified differential expression of genes that might contribute to the enhanced OA phenotype observed in the diabetic group. This study provides the first account of cartilage knee joint gene expression changes related to diabetes and the risk of OA. Understanding the relationship between diabetes and OA and the molecular changes associated with this can lead to the development of new therapeutic strategies.