scholarly journals Regulation of articular chondrocyte proliferation and differentiation by indian hedgehog and parathyroid hormone-related protein in mice

2008 ◽  
Vol 58 (12) ◽  
pp. 3788-3797 ◽  
Author(s):  
Xuesong Chen ◽  
Carolyn M. Macica ◽  
Ali Nasiri ◽  
Arthur E. Broadus
Keyword(s):  
Parathyroid Hormone ◽  
Indian Hedgehog ◽  
Related Protein ◽  
Articular Chondrocyte ◽  
Chondrocyte Proliferation ◽  
Parathyroid Hormone Related Protein ◽  
Proliferation And Differentiation

Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 543-548 ◽  
Author(s):  
S.J. Karp ◽  
E. Schipani ◽  
B. St-Jacques ◽  
J. Hunzelman ◽  
H. Kronenberg ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Critical Role ◽  
Receptor Activation ◽  
Indian Hedgehog ◽  
Appendicular Skeleton ◽  
Null Mutation ◽  
Related Protein ◽  
Chondrocyte Proliferation ◽  
Chondrocyte Hypertrophy ◽  
Parathyroid Hormone Related Protein

Indian hedgehog (Ihh) and Parathyroid Hormone-related Protein (PTHrP) play a critical role in the morphogenesis of the vertebrate skeleton. Targeted deletion of Ihh results in short-limbed dwarfism, with decreased chondrocyte proliferation and extensive hypertrophy, features shared by mutants in PTHrP and its receptor. Activation of Ihh signaling upregulates PTHrP at the articular surface and prevents chondrocyte hypertrophy in wild-type but not PTHrP null explants, suggesting that Ihh acts through PTHrP. To investigate the relationship between these factors during development of the appendicular skeleton, mice were produced with various combinations of an Ihh null mutation (Ihh(−/−)), a PTHrP null mutation (PTHrP(−/−)), and a constitutively active PTHrP/Parathyroid hormone Receptor expressed under the control of the Collagen II promoter (PTHrPR*). PTHrPR* rescues PTHrP(−/−) embryos, demonstrating this construct can completely compensate for PTHrP signalling. At 18.5 dpc, limb skeletons of Ihh, PTHrP compound mutants were identical to Ihh single mutants suggesting Ihh is necessary for PTHrP function. Expression of PTHrPR* in chondrocytes of Ihh(−/−) mice prevented premature chondrocyte hypertrophy but did not rescue either the short-limbed dwarfism or decreased chondrocyte proliferation. These experiments demonstrate that the molecular mechanism that prevents chondrocyte hypertrophy is distinct from that which drives proliferation. Ihh positively regulates PTHrP, which is sufficient to prevent chondrocyte hypertrophy and maintain a normal domain of cells competent to undergo proliferation. In contrast, Ihh is necessary for normal chondrocyte proliferation in a pathway that can not be rescued by PTHrP signaling. This identifies Ihh as a coordinator of skeletal growth and morphogenesis, and refines the role of PTHrP in mediating a subset of Ihh's actions.

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.

Parathyroid hormone-related protein (107–111) inhibits proliferation and differentiation of human bone-derived osteoblasts

Bone ◽  
1995 ◽  
Vol 17 (6) ◽  
pp. 568
Author(s):  
M.E. Martinez ◽  
A. García-Ocaña ◽  
T. del Campo ◽  
S. Medina ◽  
M. Sánchez ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Human Bone ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Proliferation And Differentiation

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.

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