Short-term effects of mechanical loading on the transdifferentiation of condylar chondrocytes

Introduction: Transdifferentiation of chondrocytes into bone cells explains most of the prenatal and early post-natal condylar growth, but its role during later postnatal growth and the mechanisms regulating transdifferentia-tion remain unknown. This study aimed to quantify the effects of mechanical loading on chondrocyte-derived osteogenesis during late postnatal condylar growth using a short-term mandibular laterotrusion model. Methods: Thirty 4-week-old Aggrecan-CreERT2 , R26RtdTomato , and 2.3Col1a1-GFP compound mice received tamoxifen injections and were divided into control and experimental groups. Appliances were bonded to shift the mandibles of the experimental mice for 5 days, causing protrusion and retrusion of the right and left condyles, respectively. Radiographic, microcomputed tomographic, and histomorphometric analyses were performed. Results: The experimental and control groups showed substantial transdifferentiation of chondro-cytes into bone cells. The experimental mice developed asymmetric mandibles, with the protrusive side signif-icantly longer than the retrusive side. The protrusive condyles showed significantly increased chondrogenesis and greater numbers of chondrocyte-derived osteogenic cells, especially in the posterior third. The opposite effects were seen on the retrusive side. Conclusions: Transdifferentiation of chondrocytes into bone cells oc-curs during late postnatal condylar growth. Laterotrusion regulates condylar chondrogenesis and chondrocyte transdifferentiation, which alters the amount and direction of condylar growth. Our study demonstrated that chon-drocytes are key players in condylar bone formation and should be the focus of studies to control and further understand condylar growth. (Am J Orthod Dentofacial Orthop 2023;164:201-14)