New Emerging Role of Pitx1 Transcription Factor in Osteoarthritis Pathogenesis

Osteoarthritis is the most common form of arthritis and the precise etiology of this disease remains unclear. We took a candidate gene-driven strategy approach based on the observation that Pitx1 transcription factor was found during hind limb development in regions giving rise to cartilage joints, long bones and skeletal muscles, while its partial in activation led to a progressive formation of osteoarthritis-like phenotype in aging Pitx1 +/− mice. To determine whether Pitx1 plays a role in osteoarthritis pathogenesis in humans, we performed an expression analysis of the pitx1 gene using RNA prepared from articular chondrocyte cultures derived from knee cartilage of patients with osteoarthritis and age- and gender-matched control subjects. Pitx1 expression was detected in articular chondrocytes derived from matched control subjects, whereas in osteoarthritic articular chondrocytes, Pitx1 expression was barely detectable by reverse transcription-polymerase chain reaction. Immunostaining with anti-Pitx1 antibodies of histologic sections of human osteoarthritic and control cartilage showed Pitx1 proteins only in the cartilage of control subjects, whereas Pitx1 proteins were hardly detected in human osteoarthritic sections. Collectively, our results uncovered an unrecognized role for Pitx1 in osteoarthritis and elucidation of the mechanism turning off its expression will clarify its pathophysiological relevance.