Soluble Mediators in Cartilage Regeneration

Abstract

Osteoarthritis (OA) is an increasing problem in orthopedics. Many factors may contribute to its development, including mechanically induced impact trauma, normal wear and tear, joint instability, but also complex age related changes and obesity. Lesions often start as a focal defect, and due to changes in homeostasis and the progressive degradation of cartilage matrix often progresses into OA. Cartilage damage causes changes in chondrocyte expression pattern that lead to increased catabolic- and decreased anabolic-processes. A lot is known about disease pathogenesis, but this has not yet resulted in an effective clinical therapy to halt OA progression and induce regeneration. Over the last years, cartilage regeneration has gained increasing attention and this has led to the identification of soluble mediators and CPCs with chondrogenic capacities in native cartilage. The combination of anabolic growth factors and stem cells has demonstrated great regenerative potential in vivo and in vitro. These observations might prove crucial in the development of new, improved OA therapies. Several challenges however remain to be solved. The underlying cause of OA can be one of many and disease progression is also dependent on many different factors including the patient’s age and lifestyle. An effective therapy will have to take into account patient specific expression profiles (‘OA phenotype’) of affected joints like e.g. relevant receptors and other anabolic and anti-catabolic factors. Based on these results, a therapy can be designed for specific subgroups or individual patients. A regenerative response to OA damage is closer than ever in this era of tissue engineering and rapid technological innovations. However, further understanding of the complex pathways that initiate and lead to progression of OA, separated by spatial and temporal expression, is necessary to improve clinically relevant OA models.