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

Abstract

Parathyroid hormone-related peptide (PTHrP) has been shown to be essential for normal endochondral bone formation. Along with Indian hedgehog (Ihh), it forms a paracrine regulatory loop that governs the pace of chondrocyte differentiation. 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 immunohistochemistry and in situ hybridization would indicate that growth plate chondrocytes themselves are the source of this peptide. The data described in this report supports the view that postnatal growth plate chondrocytes have the ability to synthesize this important regulatory peptide. Immunohistochemistry of tissue sections showed that PTHrP protein was evident throughout the chick epiphysis. PTHrP was seen in chondrocytes in the periarticular perichondrium, the perichondrium adjacent to the growth plate, the prehypertrophic zone of the growth plate, and the hypertrophic zone of the growth plate. However, cells in the proliferative zone, as well as some chondrocytes in the deeper layers of articular cartilage were predominantly negative for PTHrP. PTHrP was detected by Western blotting as a band of 16,400 Da in extracts from hypertrophic chondrocytes, but not from proliferative cells. RT-PCR detected PTHrP mRNA in both proliferative and hypertrophic growth plate chondrocytes, as well as in articular chondrocytes. PTH/PTHrP receptor mRNA was detected by Northern blotting in growth plate, but not articular chondrocytes. Thus, we conclude that most of the PTHrP present in the epiphyseal 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 addition to regulating chondrocyte differentiation.

Expression of type X collagen, Indian hedgehog and parathyroid hormone related-protein in normal and tibial dyschondroplastic chick growth plates

“…In the juvenile chick growth plate, intracellular localization of PTHrP protein was observed throughout all zones by Farquharson et al (2001a) and in the pre-hypertrophic and hypertrophic chondrocytes by Medill et al (2001). Our in situ hybridization experiments clearly localized PTHrP mRNA only to a narrow band of immature prehypertrophic chondrocytes and therefore complements the observation by Medill et al (2001) that PTHrP expression is limited to specific zones of chondrocyte maturation and supports the notion that PTHrP expression is integral to the growth plate chondrocytes in juvenile chicks. The underlying reason for the apparent discrepancies of these reported PTHrP expression patterns in the chick is at present not known.…”

“…PTHrP protein has been immunolocalized to the proliferating chondrocytes, transitional chondrocytes and the perichondrium of embryonic mouse growth plate (Lee et al, 1996). In the juvenile chick growth plate, intracellular localization of PTHrP protein was observed throughout all zones by Farquharson et al (2001a) and in the pre-hypertrophic and hypertrophic chondrocytes by Medill et al (2001). Our in situ hybridization experiments clearly localized PTHrP mRNA only to a narrow band of immature prehypertrophic chondrocytes and therefore complements the observation by Medill et al (2001) that PTHrP expression is limited to specific zones of chondrocyte maturation and supports the notion that PTHrP expression is integral to the growth plate chondrocytes in juvenile chicks.…”

“…However, if PTHrP mRNA is transiently expressed in the prehypertrophic zone it is conceivable that PTHrP is retained by the maturing cells and therefore detectable by immunohistochemistry after differentiating into hypertrophic cells. Indeed, PTHrP has not been localized within the matrix (Farquharson et al, 2001a,b;Medill et al, 2001).…”

Exploring the mechanisms regulating regeneration of deer antlers

“…Thus, although the patterns of expression of PTHrP in the developing limb and the growing antler are similar (e.g. expression in perichondrium), some distinct differences can be observed (Kartsogiannis et al 1997;Farquharson et al 2001;Medill et al 2001;Nakase et al 2001;Kindblom et al 2002). The most obvious difference is the lack of PTHrP expression in differentiated antler chondrocytes.…”

Parathyroid hormone‐related peptide and Indian hedgehog expression patterns in naturally acquired equine osteochondrosis

“…However, there is evidence that PTH-rP plays a role in the development of articular cartilage, as its expression has been shown in rat articular cartilage during the pre-and postnatal period [31] and in juvenile chickens [20]. In addition, PTHrP and PTH-rP receptor expression have been found in normal human articular cartilage, with increased levels expressed in osteoarthritis [22,30].…”