+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation



Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation



Journal of Bone and Mineral Research 15(12): 2431-2442



Hypothyroidism in children causes developmental abnormalities in bone and growth arrest, while thyrotoxicosis accelerates growth rate and advances bone age. To determine the effects of thyroid hormones on endochondral bone formation, we examined epiphyseal growth plates in control, hypothyroid, thyrotoxic, and hypothyroid-thyroxine (hypo-T4)-treated rats. Hypothyroid growth plates were grossly disorganized, contained an abnormal matrix rich in heparan sulfate, and hypertrophic chondrocyte differentiation failed to progress. These effects correlated with the absence of collagen X expression and increased parathyroid hormone-related protein (PTHrP) messenger RNA (mRNA) expression. In thyrotoxic growth plates, histology essentially was normal but PTHrP receptor (PTHrP-R) mRNA was undetectable. PTHrP is a potent inhibitor of hypertrophic chondrocyte differentiation that acts in a negative feedback loop with the secreted factor Indian hedgehog (Ihh) to regulate endochondral bone formation. Thyroid hormone receptor alpha1(TRalpha1), TRalpha2, and TRbeta1 proteins were localized to reserve zone progenitor cells and proliferating chondrocytes in euthyroid rat cartilage; regions in which PTHrP and PTHrP-R expression were affected by thyroid status. Thus, dysregulated Ihh/PTHrP feedback loop activity may be a key mechanism that underlies growth disorders in childhood thyroid disease.

(PDF emailed within 0-6 h: $19.90)

Accession: 011569339

Download citation: RISBibTeXText

PMID: 11127207

DOI: 10.1359/jbmr.2000.15.12.2431


Related references

The parathyroid hormone/parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation. Proceedings of the National Academy of Sciences of the United States of America 95(22): 13030-13035, Oct 27, 1998

Targeted expression of constitutively active receptors for parathyroid hormone and parathyroid hormone-related peptide delays endochondral bone formation and rescues mice that lack parathyroid hormone-related peptide. Proceedings of the National Academy of Sciences of the United States of America 94(25): 13689-13694, Dec 9, 1997

Targeted expression of constitutively active receptors for parathyroid hormone and parathyroid hormone-related peptide delays endochondral bone formation and rescues mice that lack parathyroid hormone-related peptide. Proceedings of the National Academy of Sciences of the United States of America 94(25): 13689-13694, 1998

Core binding factor beta (Cbfβ) controls the balance of chondrocyte proliferation and differentiation by upregulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein receptor (PPR) expression in postnatal cartilage and bone formation. Journal of Bone and Mineral Research 29(7): 1564-1574, 2015

Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor. American Journal of Physiology. Endocrinology and Metabolism 303(12): E1489-E1501, 2013

Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone development. Endocrinology 137(11): 5109-5118, 1996

A-raf and B-raf are dispensable for normal endochondral bone development, and parathyroid hormone-related peptide suppresses extracellular signal-regulated kinase activation in hypertrophic chondrocytes. Molecular and Cellular Biology 28(1): 344-357, 2007

ERK1 and ERK2 regulate chondrocyte terminal differentiation during endochondral bone formation. Journal of Bone and Mineral Research 30(5): 765-774, 2016

Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. Proceedings of the National Academy of Sciences of the United States of America 93(19): 10240-10245, 1996

The transcription factors SP1 and MAZ regulate expression of the parathyroid hormone/parathyroid hormone-related peptide receptor gene. Journal of Molecular Endocrinology 25(3): 309-319, 2000

Hormone regulation of chondrocyte differentiation and endochondral bone formation. Molecular & Cellular Endocrinology 151(1-2): 195-204, May 25, 1999

Parathyroid hormone-related peptide -dependent and -independent effects of transforming growth factor beta on endochondral bone formation. Journal of Cell Biology 145(4): 783-794, May 17, 1999

Parathyroid Hormone-Related Peptide (PTHrP)-Dependent and-Independent Effects of Transforming Growth Factor β (TGF-β) on Endochondral Bone Formation. Journal of Cell Biology 145(4): 783-794, 1999

Parathyroid hormone-related peptide (PTHrP)-dependent and -independent effects of transforming growth factor b (TGF-b) on endochondral bone formation. The Journal of Cell Biology 145(4): 3-94, 1999

Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. Journal of Cell Biology 126(6, 1): 1611-1623, 1994