The PTHrP functional domain is at the gates of endochondral bones.

PTHrP gene-expression products are generally of very low abundance. The PTHrP-lacZ knockin mouse is a useful tool in this regard, identifying PTHrP expression in previously unrecognized sites and serving to score this expression in gene-regulation experiments. These sites include the periosteum and ligament/tendon insertion sites at the surface of endochondral bones, in which PTHrP appears to regulate subjacent bone cell populations. As mesenchymal condensations chondrify, PTHrP/lacZ is also expressed in epiphyseal cartilage (the chondroepiphysis), and this structure contributes PTHrP-expressing chondrocyte populations to both articular cartilage and growth-plate cartilage when these structures take shape postnatally. The Indian hedgehog-PTHrP axis is fully deployed in both of these locations and in articular cartilage appears to protect the joint space from invasion by mineralizing cells. In most of these sites PTHrP is mechanically regulated.