Thyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86635
Title:
Thyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation.
Authors:
Robson, Helen; Siebler, Thomas; Stevens, David A; Shalet, Stephen M; Williams, Graham R
Abstract:
T3 is an important regulator of endochondral bone formation in epiphyseal growth plates. Growth arrest in juvenile hypothyroidism results from disorganization of growth plate chondrocytes and their failure to undergo hypertrophic differentiation, but it is unclear how T3 acts directly on chondrocytes or whether its actions involve other pathways. To address this issue, we investigated whether thyroid hormone receptors (TR) were localized to discrete regions of the unfused epiphysis by immunohistochemistry performed in tibial growth plates from 21-day-old rats and examined the effects of T3 on growth plate chondrocytes in agarose suspension cultures in vitro. TRalpha1, -alpha2, and -beta1 were expressed in reserve and proliferating zone chondrocytes, but not in hypertrophic cells, suggesting that progenitor cells and immature chondrocytes are the major T3 target cells in the growth plate. Chondrocytes in suspension culture expressed TRalpha1, -alpha2, and -beta1 messenger RNAs and matured by an ordered process of clonal expansion, colony formation, and terminal hypertrophic differentiation. Clonal expansion and proliferation of chondrocytes were inhibited by T3, which also induced alkaline phosphatase activity, expression of collagen X messenger RNA, and secretion of an alcian blue-positive matrix as early as 7 days after hormone stimulation. Thus, T3 inhibited chondrocyte clonal expansion and cell proliferation while simultaneously promoting hypertrophic chondrocyte differentiation. These data indicate that thyroid hormones concurrently and reciprocally regulate chondrocyte cell growth and differentiation in the endochondral growth plate.
Affiliation:
Department of Clinical Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Citation:
Thyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation. 2000, 141 (10):3887-97 Endocrinology
Journal:
Endocrinology
Issue Date:
Oct-2000
URI:
http://hdl.handle.net/10541/86635
DOI:
10.1210/en.141.10.3887
PubMed ID:
11014246
Type:
Article
Language:
en
ISSN:
0013-7227
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRobson, Helenen
dc.contributor.authorSiebler, Thomasen
dc.contributor.authorStevens, David Aen
dc.contributor.authorShalet, Stephen Men
dc.contributor.authorWilliams, Graham Ren
dc.date.accessioned2009-11-23T09:21:46Z-
dc.date.available2009-11-23T09:21:46Z-
dc.date.issued2000-10-
dc.identifier.citationThyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation. 2000, 141 (10):3887-97 Endocrinologyen
dc.identifier.issn0013-7227-
dc.identifier.pmid11014246-
dc.identifier.doi10.1210/en.141.10.3887-
dc.identifier.urihttp://hdl.handle.net/10541/86635-
dc.description.abstractT3 is an important regulator of endochondral bone formation in epiphyseal growth plates. Growth arrest in juvenile hypothyroidism results from disorganization of growth plate chondrocytes and their failure to undergo hypertrophic differentiation, but it is unclear how T3 acts directly on chondrocytes or whether its actions involve other pathways. To address this issue, we investigated whether thyroid hormone receptors (TR) were localized to discrete regions of the unfused epiphysis by immunohistochemistry performed in tibial growth plates from 21-day-old rats and examined the effects of T3 on growth plate chondrocytes in agarose suspension cultures in vitro. TRalpha1, -alpha2, and -beta1 were expressed in reserve and proliferating zone chondrocytes, but not in hypertrophic cells, suggesting that progenitor cells and immature chondrocytes are the major T3 target cells in the growth plate. Chondrocytes in suspension culture expressed TRalpha1, -alpha2, and -beta1 messenger RNAs and matured by an ordered process of clonal expansion, colony formation, and terminal hypertrophic differentiation. Clonal expansion and proliferation of chondrocytes were inhibited by T3, which also induced alkaline phosphatase activity, expression of collagen X messenger RNA, and secretion of an alcian blue-positive matrix as early as 7 days after hormone stimulation. Thus, T3 inhibited chondrocyte clonal expansion and cell proliferation while simultaneously promoting hypertrophic chondrocyte differentiation. These data indicate that thyroid hormones concurrently and reciprocally regulate chondrocyte cell growth and differentiation in the endochondral growth plate.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAnimals, Newborn-
dc.subject.meshCell Aging-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshCells, Cultured-
dc.subject.meshChondrocytes-
dc.subject.meshGrowth Plate-
dc.subject.meshHypertrophy-
dc.subject.meshMale-
dc.subject.meshRats-
dc.subject.meshRats, Sprague-Dawley-
dc.subject.meshReceptors, Thyroid Hormone-
dc.subject.meshTibia-
dc.subject.meshTriiodothyronine-
dc.titleThyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation.en
dc.typeArticleen
dc.contributor.departmentDepartment of Clinical Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.en
dc.identifier.journalEndocrinologyen
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