The parathyroid hormone-related protein and Indian hedgehog feedback loop in the growth plate
- PMID: 11277077
- DOI: 10.1002/0470846658.ch10
The parathyroid hormone-related protein and Indian hedgehog feedback loop in the growth plate
Abstract
Normal development of the growth plate requires coordinated proliferation and differentiation of chondrocytes and osteoblasts. In previous work, we have shown that Indian hedgehog (IHH), produced by prehypertrophic and hypertrophic chondrocytes, stimulates production of parathyroid hormone-related protein (PTHrP) by perichondrial and early chondrocytic cells. PTHrP then maintains chondrocytes in a proliferative, less differentiated state. Because this less differentiated state delays the production of IHH, IHH and PTHrP may participate in a negative feedback loop that synchronizes and determines the pace of differentiation of chondrocytes in the growth plate. To establish the roles of physiological levels of PTHrP and IHH, we have now injected PTH/PTHrP receptor (-/-) embryonic stem (ES) cells into normal blastocysts to generate mice with chimeric growth plates. The PTH/PTHrP receptor cells leave the proliferative cycle and differentiate prematurely in the middle of the normal proliferative columns. The columns of wild-type cells are longer than normal and the adjacent bone collar is also longer than normal. Patterns of gene expression and the use of chimeras using PTH/PTHrP receptor (-/-); IHH (-/-) ES cells suggest that modified patterns of IHH and PTHrP synthesis explain these abnormalities. Thus, IHH is a master regulator of both chondrocyte and osteoblast differentiation.
Similar articles
-
Expression of Indian hedgehog, parathyroid hormone-related protein, and their receptors in the postnatal growth plate of the rat: evidence for a locally acting growth restraining feedback loop after birth.J Bone Miner Res. 2000 Jun;15(6):1045-55. doi: 10.1359/jbmr.2000.15.6.1045. J Bone Miner Res. 2000. PMID: 10841173
-
Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein.Science. 1996 Aug 2;273(5275):613-22. doi: 10.1126/science.273.5275.613. Science. 1996. PMID: 8662546
-
The parathyroid hormone/parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation.Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13030-5. doi: 10.1073/pnas.95.22.13030. Proc Natl Acad Sci U S A. 1998. PMID: 9789035 Free PMC article.
-
PTHrP and skeletal development.Ann N Y Acad Sci. 2006 Apr;1068:1-13. doi: 10.1196/annals.1346.002. Ann N Y Acad Sci. 2006. PMID: 16831900 Review.
-
Role of parathyroid hormone-related peptide and Indian hedgehog in skeletal development.Pediatr Nephrol. 2000 Jul;14(7):606-11. doi: 10.1007/s004670000343. Pediatr Nephrol. 2000. PMID: 10912527 Review.
Cited by
-
Generation of articular chondrocytes from human pluripotent stem cells.Nat Biotechnol. 2015 Jun;33(6):638-45. doi: 10.1038/nbt.3210. Epub 2015 May 11. Nat Biotechnol. 2015. PMID: 25961409
-
Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP.J Clin Invest. 2005 Jul;115(7):1734-42. doi: 10.1172/JCI24397. Epub 2005 Jun 9. J Clin Invest. 2005. PMID: 15951842 Free PMC article.
-
Systemic Therapy for Chondrosarcoma.Curr Treat Options Oncol. 2022 Feb;23(2):199-209. doi: 10.1007/s11864-022-00951-7. Epub 2022 Feb 21. Curr Treat Options Oncol. 2022. PMID: 35190971 Review.
-
Orthopedic uses of teriparatide.Curr Osteoporos Rep. 2010 Mar;8(1):28-33. doi: 10.1007/s11914-010-0006-3. Curr Osteoporos Rep. 2010. PMID: 20425088 Review.
-
Of hedgehogs and hereditary bone tumors: re-examination of the pathogenesis of osteochondromas.Iowa Orthop J. 2003;23:87-95. Iowa Orthop J. 2003. PMID: 14575257 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Research Materials