Effects of parathyroid hormone‐related peptide on chick growth plate chondrocytes

Abstract

Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH) have similar biological effects in vitro that are mediated through the PTH receptor. PTH receptors have been demonstrated in the zone of provisional calcification and the hypertrophic zone of the cartilaginous growth plate. The current study examined the biological effects of PTHrP on chick growth plate chondrocytes. Chondrocytes were exposed to varying doses of PTHrP for 24 h, and the incorporation of radioactive thymidine into DNA was used as an index of proliferation. A dose-dependent stimulation of proliferation was seen, with a maximal 27-fold increase at 50 nM PTHrP. A dose-dependent stimulation of cAMP was seen, with a maximal effect at a dose of 50 nM. Proteoglycan synthesis, measured by incorporation of radioactive sulfate, was stimulated, with a maximal effect of 65% at 1 nM. Collagen synthesis and alkaline phosphatase activity from both cellular and matrix vesicle sources decreased in a dose-dependent fashion, with a maximal inhibition of approximately 50% of the control value. The physiologic significance of the PTH and PTHrP-responsiveness of growth plate chondrocytes is uncertain at the present time. It is possible that PTH or PTHrP, or both, act as a systemic, developmental modulator of cellular proliferation and differentiation in the growth plate.

Parathyroid hormone-related peptide expression in tibial dyschondroplasia

“…Whereas PTH functions as a systemic regulator of calcium homeostasis, PTHrP functions as a local regulator of cellular growth and differentiation , and recent experiments have confirmed that PTHrP is a negative regulator of chondrocyte terminal differentiation in longitudinal bone growth (Vortkamp et al, 1996). This is in accord with earlier studies, where PTHrP has been shown to be both a potent mitogen and an inhibitor of chondrocyte alkaline phosphatase (ALP) activity, a marker of chondrocyte terminal differentiation (Loveys et al, 1993;Henderson et al, 1996). Thus, PTHrP acts to slow the rate of differentiation of pre-hypertrophi c to hypertrophic chondrocytes within the growth plate.…”

Histomorphological and proliferative characterization of developing periosteal neochondrocytes in vitro

“…This might be accomplished using PTHrP. Recent work using gene 'knockout' mice has shown that PTHrP is essential for the normal differentiation of growth plate chondrocytes and PTHrP downregulates and delays terminal differentiation of growth plate chondrocytes [37,32,33,48,55,57]. Third, it might even be possible to induce dedifferentiation of the mature large round cell chondrocytes back into the immature small round cell chondrocytes, which might then reacquire their proliferative potential.…”

TGFβ and PTHrP Control Chondrocyte Proliferation by Activating Cyclin D1 Expression

“…Despite the recent identification of many genes that control chondrocyte proliferation and differentiation Olsen, 1997a, 1997b;Beier et al, 1999a), the intracellular signaling pathways and transcriptional mechanisms involved are not well defined. Transforming growth factor beta (TGF␤) and parathyroid hormone-related peptide (PTHrP) stimulate the proliferation of chondrocytes and chondrosarcoma cells in vitro (O'Keefe et al, 1988;Rosier et al, 1989;Guerne and Lotz, 1991;Loveys et al, 1993;Guerne et al, 1994). In addition, interruption of TGF␤ or PTHrP signaling in vivo in mice causes a reduction in the number of proliferative chondrocytes as well as premature differentiation of these cells (Amizuka et al, 1994;Karaplis et al, 1994;Serra et al, 1997;Yang et al, 2001).…”