Parathyroid hormone-related peptide expression in the epiphyseal growth plate of the juvenile chicken: Evidence for the origin of the parathyroid hormone-related peptide found in the epiphyseal growth plate

Parathyroid hormone-related peptide (PTHrP) has been shown to be essential for normal endochondral bone formation. Along with Indian hedgehog (Ihh), i t forms a paracrine regulatory loop that governs the pace of chondrocyte di fferentiation. However, the source of PTHrP for this regulatory loop is not clear. While one hypothesis has suggested the periarticular perichondrium as the source of PTHrP for growth plate regulation, other data utilizing im munohistochemistry and in situ hybridization would indicate that growth pla te chondrocytes themselves are the source of this peptide. The data describ ed in this report supports the view that postnatal growth plate chondrocyte s have the ability to synthesize this important regulatory peptide. Immunoh istochemistry of tissue sections showed that PTHrP protein was evident thro ughout the chick epiphysis. PTHrP was seen in chondrocytes in the periartic ular perichondrium, the perichondrium adjacent to the growth plate, the pre hypertrophic zone of the growth plate, and the hypertrophic zone of the gro wth plate. However, cells in the proliferative zone, as well as some chondr ocytes in the deeper layers of articular cartilage were predominantly negat ive for PTHrP. PTHrP was detected by Western blotting as a band of 16,400 D a in extracts from hypertrophic chondrocytes, but not from proliferative ce lls. RT-PCR detected PTHrP mRNA in both proliferative and hypertrophic grow th plate chondrocytes, as well as in articular chondrocytes. PTH/PTHrP rece ptor mRNA was detected by Northern blotting in growth plate, but not articu lar chondrocytes. Thus, we conclude that most of the PTHrP present in the e piphyseal growth plate of the juvenile chick originates in the growth plate itself. Furthermore, the presence of large amounts of PTHrP protein in the hypertrophic zone supports the concept that PTHrP has other functions in a ddition to regulating chondrocyte differentiation. J. Cell. Biochem. 80:504 -511, 2001. (C) 2001 Wiley-Liss, Inc.