The Role of Hemoglobin in Temporomandibular Joint Osteoarthritis and the Therapeutic Potential of Hydroxyurea.

BACKGROUND

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by articular cartilage degeneration involving chondrocyte loss and matrix degradation. However, the underlying mechanisms remain elusive. Hemoglobin (HB) has been identified in chondrocytes and is closely associated with cell survival.

OBJECTIVE

This study aims to investigate the role of HB in condylar cartilage degeneration during the early stage of TMJ OA and evaluate the potential protective effects of hydroxyurea (HU), a therapeutic agent used for sickle cell disease, suggesting its promise as a novel therapeutic strategy against OA.

METHODS

The TMJ OA model was established in 6-week-old female rats using unilateral anterior crossbite (UAC). ATDC5 chondrocytes were exposed to fluid flow shear stress (FFSS) to mimic OA-like changes in vitro. Histological and immunohistochemical staining, real-time PCR, and Western blot analysis were performed to detect the morphological and molecular changes in condylar cartilage.

RESULTS

The results showed a significant downregulation of HBA and HBB alongside cartilage degeneration in the UAC group, characterized by decreased cartilage thickness, degraded cartilage matrix, and increased matrix metalloproteinases (MMPs). FFSS-stimulated chondrocytes also exhibited decreased HBA and HBB expression. Notably, HU treatment enhanced γ-globin gene (HBG) expression, mitigated FFSS-stimulated chondrocyte degeneration in vitro, and attenuated TMJ OA progression in vivo. Specifically, HU ameliorated the degenerative phenotype in cartilage, increasing matrix content and reducing matrix-degrading enzyme expression.

CONCLUSIONS

These findings identify HB subunits as novel molecular targets for OA therapy, with HU demonstrating significant chondroprotective efficacy. The study provides mechanistic insights into OA pathogenesis and highlights a promising repurposing therapeutic strategy for clinical intervention.