RNA-seq analysis unveils differential gene expression patterns following intermittent hypoxia in the mandibular condyles of growing male rats.

Introduction: Intermittent hypoxia, which is a characteristic of obstructive sleep apnea can impair mandibular growth during early development, particularly in infants. This study aimed to investigate gene expression profiles associated with mandibular cartilage growth in infant male rats exposed to IH modeling pediatric OSA. Methods: Eight-day-old male Sprague-Dawley rats were subjected to either normoxic air or IH and sacrificed after 1 week. Mandibular growth was evaluated using micro-computed tomography and histomorphometry. RNA sequencing examined differential gene expression in bone and cartilage. Results: IH caused mandibular growth deficits, including reduced total cartilage thickness in the mid- and posterior mandibular condylar regions. Comparative measurements between IH and normoxia showed thinning of all cartilage layers in these regions under IH. In contrast, the anterior region exhibited thicker proliferative and maturative layers but a thinner hypertrophic layer under IH. RNA sequencing identified 342 upregulated and 45 downregulated genes in the IH group, including key regulators of bone and cartilage metabolism, such as gremlin-2, fibroblast growth factor 2, insulin-like growth factor binding protein 2, interleukin-1B, bone gamma-carboxyglutamate protein, wingless-related integration site 2, and SRY-box transcription factor 11. Conclusion: These findings suggest that IH alters expression of critical genes in mandibular cartilage development, potentially contributing to growth deficits.