Disrupted bone homeostasis underlies skeletal deformities in South China carp (Cyprinus rubrofuscus Lacepède, 1803): Evidence from micro-CT, transcriptomics, and histological analyses

Skeletal deformities represent a persistent challenge in aquaculture, as they compromise animal welfare and potentially affect swimming performance and production efficiency. Our previous observations revealed pronounced skeletal softening and curvature in South China carp ( Cyprinus carpio rubrofuscus ). However, the impacts of these deformities on growth performance and swimming ability, as well as the underlying causes and genetic mechanisms, remain poorly understood. In this study, micro-CT revealed markedly curled ribs accompanied by reduced bone mineral density (BMD) and bone volume (BV) in skeletal softening group. No significant difference was found either in body weight or length between normal and deformed ones by morphometric measurements. The induction velocity was significantly higher in deformed group, whereas burst swimming speed remained unaffected. Comparative transcriptomic analysis of rib tissues from two groups identified 2922 upregulated genes and 4042 downregulated genes in the deformed group. Notably, pathways related to bone metabolism and bone cell activation were significantly enriched including PI3K−Akt signaling pathway, ECM-receptor interaction and focal adhesion, suggesting a disruption of bone homeostasis in deformed fish. To validate this hypothesis, we measured the serum levels of bone formation and absorption markers, which demonstrated enhanced osteoblast activity accompanied by elevated osteoclast activity in the deformed group. Furthermore, the Masson staining of ribs and actinosts revealed more newly formed bone and less mature bone in deformed individuals, confirming an imbalance between bone formation and absorption. Collectively, our findings provide new insights into the disruption of bone homeostasis as a critical driver of abnormal bone mineralization in cultured fish.