Chondrocyte hypertrophy is a pivotal biological process in skeletal development and disease progression, with its precise regulation being essential for maintaining cartilage homeostasis and promoting tissue repair. This review systematically summarizes the molecular mechanisms of chondrocyte hypertrophy and its roles in both physiology and pathology, with a focus on its central involvement in osteoarthritis (OA), growth plate dysplasia, and heterotopic ossification. Key signaling pathways, including RUNX2, BMP, Wnt/β-catenin, and PTHrP, orchestrate hypertrophy through intricate crosstalk. Conversely, inhibitory factors such as SOX9, HIFs, and miRNAs preserve chondrocyte phenotype stability. Pathologically, dysregulated hypertrophy drives cartilage matrix degradation, metabolic reprogramming, and pro-inflammatory microenvironments, thereby exacerbating OA progression. Single-cell omics has unveiled cellular heterogeneity in OA cartilage, and innovative biomaterials combined with stem cell therapies offer promising regenerative approaches. However, limitations persist in understanding pathway interactions, replicating in vivo complexity in vitro, and translating findings to clinical applications. Future research should integrate multidisciplinary technologies to develop precise therapeutic strategies, advancing the treatment of cartilage-related disorders. This review is designed as a narrative review, aiming to systematically synthesize the molecular mechanisms, pathophysiological roles, and therapeutic implications of chondrocyte hypertrophy.
Li et al. (Mon,) studied this question.