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

The study demonstrated that overexpression of parathyroid hormone-related peptide (PTHrP) in chondrocytes led to a novel form of chondrodysplasia in mice, characterized by short-limbed dwarfism and delayed endochondral ossification. This was due to a delay 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, leaving bones that were foreshortened and misshapen but histologically near-normal. The findings confirmed PTHrP's role as an inhibitor of chondrocyte differentiation, crucial for maintaining the stepwise differentiation necessary for endochondral ossification and linear growth at the growth plate.