The role of the PTHrP/Ihh feedback loop in the unusual growth plate location in mammalian metatarsals and pisiforms

Abstract

Background

Longitudinal skeletal growth takes place in the cartilaginous growth plates. While growth plates are found at either end of conventional long bones, they occur at a variety of locations in the mammalian skeleton. For example, the metacarpals and metatarsals (MT) in the hands and feet form only a single growth plate at one end, and the pisiform in the wrist is the only carpal bone to contain a growth plate. We take advantage of this natural anatomical variation to test which components of the PTHrP/Ihh feedback loop, a fundamental regulator of chondrocyte differentiation, are specific to growth plate function.

Results

Parathyroid hormone-like hormone (Pthlh), the gene that transcribes parathyroid hormone-related peptide (PTHrP), is expressed in the reserve zone of the growth plate-forming end of the MT. At the opposite end, the absence of a PTHrP+ reserve zone results in premature chondrocyte differentiation and Indian hedgehog (Ihh) expression. Pthlh is expressed in the reserve zone of the developing pisiform, confirming the existence of a true growth plate.

Conclusion

A pool of PTHrP+ reserve zone chondrocytes is a defining characteristic of growth plates, and its patterning may be key to evolved differences in growth plate location in the mammalian skeleton.