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.
211 citations
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February 1994 in “Proceedings of the National Academy of Sciences” The study investigated the role of parathyroid hormone-related peptide (PTHrP) in hair follicle development by overexpressing it in the skin of transgenic mice using the human keratin 14 promoter. The results showed a 10-fold increase in PTHrP expression, leading to disturbances in normal hair follicle development, with mice either failing to initiate or showing delayed initiation of follicles. These findings suggested that PTHrP played a role in the early stages of hair follicle development and might be involved in regulating cellular differentiation.
478 citations
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September 1996 in “Proceedings of the National Academy of Sciences” 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.
