L. Zhong, M. Karperien, J.N. Post
Osteoarthritis (OA) is a multifactorial disease characterized by progressive degradation of articular cartilage leading to loss of joint function. It affects several million people in the world. Currently there is no cure for OA. In a subset of patients OA is associated with hypertrophic differentiation of articular chondrocytes. This process normally occurs in the growth plate. Healthy articular cartilage is protected against hypertrophy. Our group identified DKK1, FRZB (WNT antagonists) and GREM1 (BMP antagonist) as the natural brakes on hypertrophic differentiation and regulation of the maintenance of the articular phenotype. Moreover, we previously demonstrated that decreased production of DKK1, FRZB, GREM1 in human chondrocytes has been associated with cartilage hypertrophy in OA. In this project, we hypothesize that DKK1, FRZB, GREM1 are the gatekeepers for the maintenance of homeostasis in articular cartilage. To prove this, we investigated whether knockdown of DKK1, FRZB and GREM1 is sufficient to cause hypertrophic differentiation in healthy articular chondrocytes. Furthermore, we investigated the influence of catabolic factors such as interleukin-1β (IL-1β) on the gene transcription levels of DKK1, FRZB, GREM1. We found that the presence of DKK1, FRZB and GREM1 is sufficient to inhibit the catabolic effects of IL-1β.