• Please log in or register to access this feature.

Research Article

You have full text access to this OnlineOpen article

Thyroid Hormones Regulate Hypertrophic Chondrocyte Differentiation and Expression of Parathyroid Hormone-Related Peptide and Its Receptor During Endochondral Bone Formation†

  1. David A. Stevens1,
  2. Robert P. Hasserjian2,
  3. Helen Robson3,
  4. Thomas Siebler3,
  5. Stephen M. Shalet4,
  6. Graham R. Williams1,*

Article first published online: 1 DEC 2000

DOI: 10.1359/jbmr.2000.15.12.2431

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 15, Issue 12, pages 2431–2442, December 2000

Additional Information

How to Cite

Stevens, D. A., Hasserjian, R. P., Robson, H., Siebler, T., Shalet, S. M. and Williams, G. R. (2000), Thyroid Hormones Regulate Hypertrophic Chondrocyte Differentiation and Expression of Parathyroid Hormone-Related Peptide and Its Receptor During Endochondral Bone Formation. J Bone Miner Res, 15: 2431–2442. doi: 10.1359/jbmr.2000.15.12.2431

Author Information

  1. 1

    Imperial College School of Medicine Molecular Endocrinology Group, Division of Medicine and Medical Research Council Clinical Sciences Center, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom

  2. 2

    Department of Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom

  3. 3

    Department of Clinical Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom

  4. 4

    Department of Endocrinology, Christie Hospital National Health Service Trust, Manchester, United Kingdom

*Address reprint requests to: Dr. Graham R. Williams, ICSM Molecular Endocrinology Group, MRC Clinical Sciences Center, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K.

  1. †

    This paper was presented in part at the 72nd Annual Meeting of the American Thyroid Association, Palm Beach, Florida, U.S.A., 1999

Publication History

  1. Issue published online: 2 DEC 2009
  2. Article first published online: 1 DEC 2000
  3. Manuscript Accepted: 27 JUN 2000
  4. Manuscript Revised: 17 MAY 2000
  5. Manuscript Received: 13 JAN 2000

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (3634K)

Keywords:

  • thyroid hormone;
  • parathyroid hormone-related peptide;
  • parathyroid hormone-related peptide receptor;
  • endochondral bone formation;
  • growth plate chondrocytes

Abstract

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 α1(TRα1), TRα2, and TRβ1 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.

View Full Article (HTML) Get PDF (3634K)