Ovariectomy selectively reduces the concentration of transforming growth factor β in rat bone

Implications for estrogen deficiency-associated bone loss

R. D. Finkelman, N. H. Bell, D. D. Strong, Laurence Demers, D. J. Baylink

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Previous work showed that production of transforming growth factor β (TGF-β) by osteoblast-like rat UMR 106 cells was increased by 17β-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-β in rat long bones, female Sprague-Dawley rats were either sham-operated (n = 19) or ovariectomized (n = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25- dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from sham-operated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of TGF-β in bone but did not change the concentration of insulin-like growth factors I or II compared with values in bone from control animals. The reduction of bone TGF-β was evident 6 weeks after surgery but not at 3 weeks. Treatment of ovariectomized rats with estrogen eliminated the TGF-β deficit. To determine whether 17β-estradiol increased TGF-β production by normal bone cells, mouse osteoblasts were treated for 2 days with 17β-estradiol. The production of TGF-β was increased almost 2-fold by 1 nM 17β-estradiol, and short-term treatment stimulated the intracellular accumulation of TGF-β1 mRNA. We conclude that ovariectomy reduces deposition of TGF-β in rat bone and that diminished skeletal TGF-β could play a role in the pathogenesis of bone loss, fractures, and microfractures that occur in estrogen-deficient states. Our results support the possibility that estrogen and bone TGF-β may be necessary for normal maintenance of the skeleton in female rats.

Original languageEnglish (US)
Pages (from-to)12190-12193
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number24
DOIs
StatePublished - Dec 1 1992

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Transforming Growth Factors
Ovariectomy
Estrogens
Bone and Bones
Estradiol
Bone Development
Serum
Osteoblasts
Diaphyses
Stress Fractures
Insulin-Like Growth Factor II
Hydroxyproline
Bone Fractures
Thigh
Insulin-Like Growth Factor I
Skeleton
Magnesium
Sprague Dawley Rats
Body Weight
Maintenance

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Ovariectomy selectively reduces the concentration of transforming growth factor β in rat bone: Implications for estrogen deficiency-associated bone loss",
abstract = "Previous work showed that production of transforming growth factor β (TGF-β) by osteoblast-like rat UMR 106 cells was increased by 17β-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-β in rat long bones, female Sprague-Dawley rats were either sham-operated (n = 19) or ovariectomized (n = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25- dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from sham-operated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of TGF-β in bone but did not change the concentration of insulin-like growth factors I or II compared with values in bone from control animals. The reduction of bone TGF-β was evident 6 weeks after surgery but not at 3 weeks. Treatment of ovariectomized rats with estrogen eliminated the TGF-β deficit. To determine whether 17β-estradiol increased TGF-β production by normal bone cells, mouse osteoblasts were treated for 2 days with 17β-estradiol. The production of TGF-β was increased almost 2-fold by 1 nM 17β-estradiol, and short-term treatment stimulated the intracellular accumulation of TGF-β1 mRNA. We conclude that ovariectomy reduces deposition of TGF-β in rat bone and that diminished skeletal TGF-β could play a role in the pathogenesis of bone loss, fractures, and microfractures that occur in estrogen-deficient states. Our results support the possibility that estrogen and bone TGF-β may be necessary for normal maintenance of the skeleton in female rats.",
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Ovariectomy selectively reduces the concentration of transforming growth factor β in rat bone : Implications for estrogen deficiency-associated bone loss. / Finkelman, R. D.; Bell, N. H.; Strong, D. D.; Demers, Laurence; Baylink, D. J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 24, 01.12.1992, p. 12190-12193.

Research output: Contribution to journalArticle

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