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

Abstract

Transdifferentiation of chondrocytes into bone cells explains most of the prenatal and early postnatal condylar growth, but its role during later postnatal growth and the mechanisms regulating transdifferentiation 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. 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. The experimental and control groups showed substantial transdifferentiation of chondrocytes into bone cells. The experimental mice developed asymmetric mandibles, with the protrusive side significantly 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. Transdifferentiation of chondrocytes into bone cells occurs 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 chondrocytes are key players in condylar bone formation and should be the focus of studies to control and further understand condylar growth.