Combined effects of unilateral nasal obstruction and occlusal bite-raising on mandibular condylar development in growing rats

Background Unilateral nasal obstruction (UNO) alters mandibular condylar growth, while bite-raising increases mechanical loading on the temporomandibular joint (TMJ). Hypoxia induced by UNO may exacerbate TMJ osteoarthritis (TMJOA)—like changes associated with occlusal disturbances during growth, and understanding their combined effects is clinically relevant. This study aimed to investigate whether UNO and bite-raising synergistically contribute to TMJ osteoarthritis (TMJOA)–like changes in growing rats. Methods Twenty-four 4-week-old male Wistar rats were randomly divided into four groups: control, bite-raising (iOVD; 2-mm composite resin on the upper molars), UNO (complete left nostril sutured), and combined group (iOVD + UNO). Micro-CT was used to assess mandibular morphology and trabecular structure. Histological and immunohistochemical analyses were performed to evaluate cartilage degeneration, bone remodeling, and extracellular matrix changes. Gene expression levels of HIF-1α, IL-1β, IL-6, NF-κB, TGF-β1, and Postn were analyzed by qPCR. Results At 9 weeks, SpO2 was significantly reduced in the UNO and iOVD + UNO groups. Micro-CT revealed increased trabecular separation and decreased bone volume fraction in the iOVD + UNO group, with suppressed bone formation and enhanced resorption confirmed by TRAP/ALP staining. Histology showed cartilage degeneration and reduced proteoglycans in all experimental groups, most pronounced in the iOVD + UNO group. Immunohistochemistry demonstrated increased expression of HIF-1α, MMP-13, and Postn, and decreased type II collagen in the iOVD + UNO group. qPCR analysis revealed elevated mRNA expression of HIF-1α, IL-1β, NF-κB, and Postn in the iOVD + UNO group. Conclusion These findings suggest that the combination of nasal obstruction and bite-raising exacerbates the disruption of cartilage homeostasis and subchondral bone remodeling in the mandibular condyle, contributing to TMJOA-like structural and biological changes in growing rats.