Cartilage degeneration is associated with activation of the PI3K/AKT signaling pathway in a growing rat experimental model of developmental trochlear dysplasia.

Introduction: Trochlear dysplasia is a commonly encountered lower extremity deformity in humans. However, the molecular mechanism of cartilage degeneration in trochlear dysplasia is unclear thus far.

Objectives: The PI3K/AKT signaling pathway is known to be important for regulating the pathophysiology of cartilage degeneration. The aim of this study was to investigate the relationship of the PI3K/AKT signaling pathway with trochlear dysplasia cartilage degeneration.

Methods: In total, 120 female Sprague-Dawley rats (4 weeks of age) were randomly separated into control and experimental groups. Distal femurs were isolated from the experimental group at 4, 8, and 12 weeks after surgery; they were isolated from the control group at the same time points. Micro-computed tomography and histological examination were performed to investigate trochlear anatomy and changes in trochlear cartilage. Subsequently, expression patterns of PI3K/AKT, TGFβ1, and ADAMTS-4 in cartilage were investigated by immunohistochemistry and quantitative polymerase chain reaction.

Results: In the experimental group, the trochlear dysplasia model was successfully established at 8 weeks after surgery. Moreover, cartilage degeneration was observed beginning at 8 weeks after surgery, with higher protein and mRNA expression levels of PI3K/AKT, TGFβ1, and ADAMTS-4, relative to the control group.

Conclusion: Patellar instability might lead to trochlear dysplasia in growing rats. Moreover, trochlear dysplasia may cause patellofemoral osteoarthritis; cartilage degeneration in trochlear dysplasia might be associated with activation of the PI3K/AKT signaling pathway. These results provide insights regarding the high incidence of osteoarthritis in patients with trochlear dysplasia. However, more research is needed to clarify the underlying mechanisms.