Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria.

Tashjian, Armen H.; Voelkel, Edward F.; Lazzaro, Maribeth A.; Singer, Frederick R.; Roberts, Anita B.; Derynck, Rik; Winkler, Moritz; Levine, Lawrence

doi:10.1073/pnas.82.13.4535

Cited by 334 publications

(95 citation statements)

References 28 publications

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“…In addition, the ability of TGFa and EGF to indirectly stimulate bone-resorbing activity has long been described (Tashjian et al 1985, Ibbotson et al 1986. Several previous studies have also shown expression of EGFR in BMSCs and in osteoblast-like cells, as well as biological effects of EGF and/or TGFa in osteoblasts (Ibbotson et al 1986, Drake et al 1994, Sodek et al 1995, Satomura et al 1998.…”

Section: Discussionmentioning

confidence: 99%

Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis

Normanno¹

2005

Endocrine Related Cancer

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Significant relief of bone pain in patients with bone metastases was observed in a clinical trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in breast cancer. Osteoclast activation and differentiation are regulated by bone marrow stromal cells (BMSC), a heterogeneous cell compartment that comprehends undifferentiated mesenchymal stem cells (MSC) and their specialized progeny. In this regard, we found that human primary BMSCs express immunoreactive EGFR. Expression of EGFR mRNA and protein was also demonstrated in two human, continuous MSC-like cell lines, HDS-1 and HDS-2 cells. Treatment of HDS cells with EGF produced a significant increase in the levels of activated EGFR which was not observed in the presence of gefitinib. A significant reduction in the basal levels of activation of the EGFR and of Akt was observed in HDS cells following treatment with gefitinib. Treatment of HDS cells with gefitinib produced a significant reduction in the levels of secreted macrophage colony-stimulating factor (M-CSF) and cell-associated receptor activator of NF-kB ligand (RANKL) in both cell lines, as assessed by using specific ELISA and Western blotting techniques. Finally, the ability to sustain the differentiation of pre-osteoclasts of conditioned medium from gefitinib-treated HDS cells was reduced by approximately 45% as compared with untreated HDS cells. These data have demonstrated for the first time that the EGFR regulates the ability of BMSCs to induce osteoclast differentiation and strongly support clinical trials of gefitinib in breast cancer patients with bone disease.

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Section: Discussionmentioning

confidence: 99%

Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis

Normanno¹

2005

Endocrine Related Cancer

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“…The increased potency of milrinone in mouse calvaria compared with the fetal rat limb bones may be explained as a result of the effect being mediated by prostaglandin production in the calvaria. Several agents, including epidermal growth factor (18,19), transforming growth factor (20,21), potassium (15), and thrombin (13), whose effect on bone resorption is mediated by endogenous prostaglandin production exhibit different potencies in limb bones and calvaria.…”

Section: Discussionmentioning

confidence: 99%

Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture.

Krieger¹,

Stappenbeck²,

Stern³

1987

J. Clin. Invest.

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MethodsThe cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones. Threshold doses were 0.1 l&M in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations below 0.1 mM did not affect calvarial cyclic AMP. 0.5 luM indomethacin inhibited milne effects in calvaria but usually not in limb bones. 3 nM calcitonin inhibited milrinone-stimulated resorption and there was no escape from this inhibition. Structural homology between milrinone and thyroxine has been reported. We find similarities between milrinone and thyroxine actions on bone, because prostaglandin production was crucial for the effects of both agents in calvaria but not in limb bones, and neither agent exhibited escape from calcitonin inhibition.

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“…The relative composition of bone is presented in the Table 1, while the most important biomedical properties of the bones are presented in Table2. The in vivo bone biosynthesis is controlled by many factors such as: BMP (bone morphogenetic proteins) (Abe et al 2000), transforming growth factors (Tashjian et al 1985), cytokines (de Vernejoul et al 1993 ), hormones (Bollerslev et al 1991 ; www.intechopen.com Advances in Collagen/Hydroxyapatite Composite Materials 5 1990; Hock and Gera 1992), transcription factors Ogawa et al 2000), adhesion molecules (Miyake et al 1991) and so on.…”

mentioning

confidence: 99%