1,25-Dihydroxyvitamin D3—mediated transforming growth factor-β release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiencies
Corresponding Author
Jozien G. H. Sterck Ph.D.
Department of Endocrinology, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands
ACTA-Vrije Universiteit Department of Oral Cell Biology Van der Boechorststraat 7 1081 BT Amsterdam, The NetherlandsSearch for more papers by this authorJenneke Klein-Nulend
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands
Search for more papers by this authorElisabeth H. Burger
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands
Search for more papers by this authorPaul Lips
Department of Endocrinology, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands
Search for more papers by this authorCorresponding Author
Jozien G. H. Sterck Ph.D.
Department of Endocrinology, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands
ACTA-Vrije Universiteit Department of Oral Cell Biology Van der Boechorststraat 7 1081 BT Amsterdam, The NetherlandsSearch for more papers by this authorJenneke Klein-Nulend
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands
Search for more papers by this authorElisabeth H. Burger
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands
Search for more papers by this authorPaul Lips
Department of Endocrinology, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands
Search for more papers by this authorAbstract
To evaluate the osteoblastic function in patients with multiple pituitary hormone deficiencies (M-PHD) and with isolated growth hormone deficiency (I-GHD), bone cells were cultured and the effects of 10−8 M 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) on parameters of cell proliferation, osteoblastic differentiation, and local paracrine regulation were measured. Three days of 1,25(OH)2D3 treatment increased alkaline phosphatase activity and osteocalcin release but inhibited [3H]thymidine incorporation in all cell cultures from patients as well as from controls. In addition, 1,25(OH)2D3 increased the release of both total and active transforming growth factor-β (TGF-β) in bone cells from controls by, respectively, 4.9- and 3.2-fold and in bone cells from I-GHD by 5.1- and 1.5-fold, respectively. However, in bone cells from M-PHD, the stimulation of total TGF-β release was significantly lower (1.3-fold) than in control and I-GHD cells, and active TGF-β release was not stimulated at all. One year of supplementation with human growth hormone did not improve this deficient TGF-β release in bone cells from M-PHD. We conclude that cultured bone cells from I-GHD and M-PHD show a normal response to 1,25(OH)2D3 regarding cell proliferation and osteoblastic differentiation, which implicates a normal l,25(OH)2D3-receptor function. In cells from controls and I-GHD, 1,25(OH)2D3 enhanced both total and active TGF-β release. However, bone cells from M-PHD showed a deficient TGF-β response to 1,25(OH)2D3. These results suggest that the regulation of TGF-β production is a major paracrine factor involved in hypopituitarism.
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