Combination Radioprotectors Maintain Proliferation Better than Single Agents by Decreasing Early Parathyroid Hormone-Related Protein Changes after Growth Plate Irradiation

2006 ◽  
Vol 165 (3) ◽  
pp. 350-358 ◽  
Author(s):  
Timothy A. Damron ◽  
Jason A. Horton ◽  
Asghar Naqvi ◽  
Richard M. Loomis ◽  
Bryan S. Margulies ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Growth Plate ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Better Than

scholarly journals Organization of the Indian hedgehog – parathyroid hormone-related protein system in the postnatal growth plate

2011 ◽  
Vol 47 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Michael Chau ◽  
Patricia Forcinito ◽  
Anenisia C Andrade ◽  
Anita Hegde ◽  
Sohyun Ahn ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Growth Plate ◽  
Feedback Loop ◽  
Postnatal Growth ◽  
Indian Hedgehog ◽  
Related Protein ◽  
Functional Changes ◽  
Growth Cartilage ◽  
Embryonic Growth ◽  
Parathyroid Hormone Related Protein

In embryonic growth cartilage, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte differentiation. Postnatally, this region undergoes major structural and functional changes. To explore the organization of the Ihh–PTHrP system in postnatal growth plate, we microdissected growth plates of 7-day-old rats into their constituent zones and assessed expression of genes participating in the Ihh–PTHrP feedback loop.Ihh, Patched 1, Smoothened,Gli1, Gli2, Gli3, andPthr1were expressed in regions analogous to the expression domains in embryonic growth cartilage. However, PTHrP was expressed in resting zone cartilage, a site that differs from the embryonic source, the periarticular cells. We then used mice in whichlacZhas replaced coding sequences ofGli1and thus serves as a marker for active hedgehog signaling. At 1, 4, 8, and 12 weeks of age,lacZexpression was detected in a pattern analogous to that of embryonic cartilage. The findings support the hypothesis that the embryonic Ihh–PTHrP feedback loop is maintained in the postnatal growth plate except that the source of PTHrP has shifted to a more proximal location in the resting zone.

scholarly journals Expression and localization of Indian hedgehog (Ihh) and parathyroid hormone related protein (PTHrP) in the human growth plate during pubertal development

2002 ◽  
Vol 174 (2) ◽  
pp. R1-R6 ◽  
Author(s):  
JM Kindblom ◽  
O Nilsson ◽  
T Hurme ◽  
C Ohlsson ◽  
L Savendahl
Keyword(s):  
Parathyroid Hormone ◽  
Growth Plate ◽  
Pubertal Development ◽  
Human Growth ◽  
Indian Hedgehog ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Cartilage Differentiation ◽  
Pubertal Stages

Indian Hedgehog (Ihh) has been reported to control the rate of cartilage differentiation during skeletal morphogenesis in rodents through a negative feedback loop involving parathyroid hormone related protein (PTHrP). The role of Ihh and PTHrP in the regulation of human epiphyseal chondrocytes is unknown. The aim of the current study was to examine the expression and localization of Ihh and PTHrP in the human growth plate at various pubertal stages. Growth plate biopsies were obtained from patients subjected to epiphyseal surgery and the expression of Ihh and PTHrP was detected by immunohistochemistry. We show that Ihh and PTHrP are expressed mainly in early hypertrophic chondrocytes in the human growth plate. The levels of expression of Ihh and PTHrP are higher in early stages of puberty than later. Our results suggest that Ihh and PTHrP are present in the human growth plate and that Ihh and PTHrP may be involved in the regulation of pubertal growth in humans.

scholarly journals Parathyroid hormone/parathyroid hormone-related protein receptor signaling is required for maintenance of the growth plate in postnatal life

2010 ◽  
Vol 108 (1) ◽  
pp. 191-196 ◽  
Author(s):  
Takao Hirai ◽  
Andrei S. Chagin ◽  
Tatsuya Kobayashi ◽  
Susan Mackem ◽  
Henry M. Kronenberg
Keyword(s):  
Parathyroid Hormone ◽  
Growth Plate ◽  
Physiological Role ◽  
Postnatal Growth ◽  
Mitochondrial Pathway ◽  
Chondrocyte Apoptosis ◽  
Postnatal Life ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

Parathyroid hormone (PTH)-related protein (PTHrP), regulated by Indian hedgehog and acting through the PTH/PTHrP receptor (PPR), is crucial for normal cartilage development. These observations suggest a possible role of PPR signaling in the postnatal growth plate; however, the role of PPR signaling in postnatal chondrocytes is unknown. In this study, we have generated tamoxifen-inducible and cartilage-specific PPR KO mice to evaluate the physiological role of PPR signaling in postnatal chondrocytes. We found that inactivation of the PPR in chondrocytes postnatally leads to accelerated differentiation of chondrocytes, followed by disappearance of the growth plate. We also observed an increase of TUNEL-positive cells and activities of caspase-3 and caspase-9 in the growth plate, along with a decrease in phosphorylation of Bad at Ser155 in postnatal PPR KO mice. Administration of a low-phosphate diet, which prevents apoptosis of chondrocytes, prevented the disappearance of the growth plate. Taken together, these observations suggest that the major consequences of PPR activation are similar in both the fetal and postnatal growth plates. Moreover, chondrocyte apoptosis through the activation of a mitochondrial pathway may be involved in the process of premature disappearance of the growth plate by postnatal inactivation of the PPR in chondrocytes.

Parathyroid hormone-related protein is induced by hypoxia and promotes expression of the differentiated phenotype of human articular chondrocytes

2013 ◽  
Vol 125 (10) ◽  
pp. 461-470 ◽  
Author(s):  
Michele Pelosi ◽  
Stefano Lazzarano ◽  
Brendan L. Thoms ◽  
Chris L. Murphy
Keyword(s):  
Parathyroid Hormone ◽  
Articular Cartilage ◽  
Growth Plate ◽  
Articular Chondrocytes ◽  
Human Articular Chondrocytes ◽  
Long Bone ◽  
Human Articular Cartilage ◽  
Dependent Manner ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

PTHrP (parathyroid hormone-related protein) is crucial for normal cartilage development and long bone growth and acts to delay chondrocyte hypertrophy and terminal differentiation in the growth plate. After growth plate closure adult HACs (human articular chondrocytes) still produce PTHrP, suggesting a possible role for this factor in the permanent articular cartilage. However, the expression regulation and function of PTHrP in the permanent articular cartilage is unknown. Human articular cartilage is an avascular tissue and functions in a hypoxic environment. The resident chondrocytes have adapted to hypoxia and use it to drive their tissue-specific functions. In the present study, we explored directly in normal articular chondrocytes isolated from a range of human donors the effect of hypoxia on PTHrP expression and whether PTHrP can regulate the expression of the permanent articular chondrocyte phenotype. We show that in HACs PTHrP is up-regulated by hypoxia in a HIF (hypoxia-inducible factor)-1α and HIF-2α-dependent manner. Using recombinant PTHrP, siRNA-mediated depletion of endogenous PTHrP and by blocking signalling through its receptor [PTHR1 (PTHrP receptor 1)], we show that hypoxia-induced PTHrP is a positive regulator of the key cartilage transcription factor SOX9 [SRY (sex determining region on the Y chromosome)-box 9], leading to increased COL2A1 (collagen type II, α1) expression. Our findings thus identify PTHrP as a potential factor for cartilage repair therapies through its ability to promote the differentiated HAC phenotype.

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