A potential role of homeobox transcription factors in osteoarthritis

When a healthy joint progressively becomes osteoarthritic, the structures of the affected cartilage, bone and synovia undergo an initial phase of rearrangement. The exact molecular and cellular events occurring in this early osteoarthritic transition phase still remain elusive. Homeobox (Hox) genes encode for transcription factors that typically regulate limb morphogenesis and skeletal formation during development. More recently they were shown to be required for tissue remodelling and homeostasis in adults and to be modulated in a variety of pathologies. Here we present and discuss the hypothesis that dysregulation of specific Hox genes is associated with the onset and development of osteoarthritis (OA). Discovering mechanisms modulating Hox gene expression could not only provide important information in understanding OA pathology and its initiation, but also help to identify biomarkers reflecting the state of early OA. This knowledge would allow anticipating the time window for clinical treatment of the affected cartilage and assist in the development of innovative strategies to restore joint homeostasis, e.g., by cell or gene therapy.