Role of HIF-1α and HIF-2α in osteoarthritis

The hallmark of OA is cartilage destruction, several factors such as catabolic enzymes and chondrocyte death include apoptosis and/or autophagy are considered for the pathogenesis. Articular cartilage is maintained in a low oxygen environment throughout life. Chondrocytes are therefore adapted to these hypoxic conditions. The increased HIF-1 alpha and HIF-2 alpha mediate the response of chondrocytes to hypoxia. HIF-la regulates chondrogenesis by regulating SOX9 expression in the genetic level, HIF-1 also serves to regulate both autophagy and apoptosis. Therefore, HIF-1 alpha may protect articular cartilage by promoting the chondrocyte phenotype, maintaining chondrocyte viability, and supporting metabolic adaptation to a hypoxic environment. In contrast with HIF-la, HIF-2 alpha is a catabolic factor in the osteoarthritic process. Although HIF-2 alpha is essential for hypoxic induction of the human articular chondrocyte phenotype, HIF-2 alpha directly induces the expression of catabolic factors in chondrocytes, and HIF-2 alpha enhances Fas expression to mediate chondrocyte apoptosis and regulates autophagy in maturing chondrocytes. Taken together, manipulation of HIF-la and HIF-2 alpha could represent a promising approach to the treatment of OA. Further study should elucidate the exact machnism of HIF-1 alpha and HIF-2 alpha in cartilage and determine which is predominant in osteoarthritic process. (C) 2014 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.