We have created a PTHrP-lacZ knock-in mouse, which serves as a sensitivePTHrP gene expression system. Findings in this mouse suggest that existinginterpretations as to PTHrP functions in endochondral bone may need to be refined.The chondroepiphysis (CE) is the primordial epiphyseal growth zone in lowerforms such as teleosts and is also the structure that drives linear growth duringembryogenesis in terrestrial mammals. The proliferative chondrocytes of the CEexpress PTHrP, and it is this stage of prenatal development that has been focused uponalmost exclusively in the published work. At postnatal day 7-10 in the mouse, thesecondary ossification center forms and subdivides the PTHrP-expressing chondrocytesinto two subpopulations, one associated with the growth plate and a second that willbecome articular chondrocytes (AC). The PTH-1 receptor-expressing prehypertrophicchondrocytes lie immediately subjacent to the PTHrP-expressing ACs, in a fashion thatexcludes mineralizing hypertrophic chondrocytes from the ACs and joint space. PTHrPexpression in ACs is load-depend, and unloading a joint in vivo leads to a suppressionin PTHrP/(3 gal expression and a large increase in hypertrophic chondrocytes thatapproach the articular surface.We propose here to conditionally delete PTHrP in ACs using a Gdf5-Cre mouse.This system will allow a detailed study of the working hypothesis that PTHrP normallyfunctions to regulate the chondrocyte differentiation program in ACs, as it doeselsewhere. The system may also provide a valuable mouse model of osteoarthritis.
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