The Effects of Dietary Loading on Chondrocytes Transdifferentiation During Postnatal Maxillary Growth

ABSTRACT Background The mid‐palatal suture is a key growth site for transverse maxillary expansion, yet the cellular mechanisms governing its postnatal development and response to mechanical loading remain poorly defined. This study investigated the contribution of chondrocyte‐derived osteogenesis to maxillary bone formation and the influence of dietary loading on this process. Methods Two chondrocyte‐lineage tracing mouse models were utilised: Aggrecan‐Cre ERT2 (Acan Lineage ); R26R TdTomato ; 2.3Col1a1‐GFP and Col10a1‐Cre (Col10a1 Lineage ); R26R TdTomato ; 2.3Col1a1‐GFP. Twelve 3‐week‐old male mice per genotype were randomly assigned to either a hard diet (control) or soft diet (experimental) for 6 weeks. A single tamoxifen injection was administered to Acan Lineage mice at 3 weeks to induce Cre event. Radiographic, uCT and histomorphometric analyses were performed. Results Soft diet feeding significantly reduced maxillary arch width, bone volume and bone mineral density in the mid‐palatal region. Although chondrocyte proliferation was comparable between groups, differentiation was notably impaired. Lineage tracing demonstrated that both Acan Lineage ‐ and Col10a1 Lineage ‐derived bone cells were more abundant under hard diet conditions, while non‐chondrocyte‐derived bone cell numbers remained similar between groups. The population of Acan Lineage ‐derived pre‐osteoblasts and osteocytes was markedly lower in soft diet‐fed mice. Conclusions Acan + chondrocytes in the mid‐palatal suture contribute to postnatal maxillary bone formation through transdifferentiation. Dietary mechanical loading regulates both chondrogenesis and chondrocyte transdifferentiation, ultimately affecting maxillary bone growth and remodelling.