Targeted Overexpression of Parathyroid Hormone-Related Peptide in Chondrocytes Causes Chondrodysplasia and Delayed Endochondral Bone Formation

The study investigated the effects of overexpressing parathyroid hormone-related peptide (PTHrP) in chondrocytes using a mouse model. It was found that this overexpression led to a form of chondrodysplasia, characterized by short-limbed dwarfism and delayed endochondral ossification. The delay was due to a postponement in chondrocyte differentiation and bone collar formation, resulting in mice being born with a cartilaginous endochondral skeleton. Initially, chondrocytes became hypertrophic at the periphery of developing long bones, reversing the typical pattern of differentiation and ossification. By 7 weeks, these delays were mostly corrected, although the bones remained foreshortened and misshapen. The findings confirmed that PTHrP acted as an inhibitor of chondrocyte differentiation, playing a crucial role in maintaining the stepwise differentiation necessary for endochondral ossification and linear growth at the growth plate.