Endogenous GM-CSF is involved as an autocrine growth factor for human osteoblastic cells

Modrowski, Dominique; Lomri, Abderrahim; Marie, Pierre J.

doi:10.1002/(sici)1097-4652(199701)170:1<35::aid-jcp5>3.0.co;2-m

Cited by 25 publications

(14 citation statements)

References 31 publications

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“…The cells were cultured in serum-free medium in the presence or absence of AS or R oligonucleotides alone for 2 days, and then rhGM-CSF and/or heparin or FCS were added for 3 days. Consistent with our previous findings (31,32), hOB cells proliferated in the absence of exogenous mitogenic factors, and the basal proliferation rate was enhanced in the presence of rhGM-CSF. The rate of proliferation was similar in R-treated cells and in cells cultured in the absence of oligonucleotides.…”

Section: Fig 4 Co-immunoprecipitation Of Gmr␣ and Syndecan-2supporting

confidence: 92%

“…The effect of syndecan-2 inhibition on the expression of GM-CSF receptor was also examined by immunochemistry in the same conditions. To assess that AS effectively reduced syndecan-2 levels, we used a quantitative method previously shown to be accurate in determining precise changes in protein levels under AS treatment (31,38). The number of cells expressing syndecan-2, GMR␣, and GMR␤ in the presence of AS or R oligonucleotides was counted in 3-4 wells, and the results were reported as % of total number of cells.…”

Section: Methodsmentioning

confidence: 99%

“…Exogenous GM-CSF stimulates human osteoblast-like cell growth and antagonizes the induction by 1,25-dihydroxyvitamin D of osteocalcin and alkaline phosphatase activity (30). We previously showed that GM-CSF is an autocrine growth factor for normal human osteoblastic cells (31). We subsequently found that GM-CSF not only binds to HSPG expressed at the osteoblastic cell surface but that the mitogenic activity of GM-CSF is dependent on the presence of fully sulfated PGs in these cells (32).…”

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confidence: 99%

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Syndecan-2 Is Involved in the Mitogenic Activity and Signaling of Granulocyte-Macrophage Colony-stimulating Factor in Osteoblasts

Modrowski¹,

Basle²,

Lomri³

et al. 2000

Journal of Biological Chemistry

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We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) binds to heparan sulfate proteoglycans expressed at the surface of osteoblastic cells and that the mitogenic activity of this cytokine is dependent on the presence of fully sulfated proteoglycans. In this study, we determined if GM-CSF interacts with syndecans, a family of cell surface heparan sulfate proteoglycans. Human primary osteoblasts were found to express syndecan-2 and -4 but few syndecan-1 transcripts and proteins. Recombinant human GM-CSF coupled to biotin was found to bind to syndecan-2. Immunocytochemical transmission electron microscope analysis showed co-localization of syndecan-2 and GM-CSF at the cell membrane surface. Syndecan-2 also co-localized at the cell surface and co-immunoprecipitated with the GM-CSF receptor ␣ chain, suggesting a strong interaction between the cytokine, its receptor, and syndecan-2. Phosphorylation of tyrosine residues in syndecan-2 associated with the ␣ chain of the GM-CSF receptor was increased after cell stimulation by GM-CSF. Antisense oligonucleotides that reduced specifically the expression of syndecan-2 inhibited the mitogenic activity of GM-CSF and the activation of extracellular signal-regulated kinase-1 induced by the cytokine. Our results indicate functional interactions between syndecan-2 and GM-CSF in osteoblasts, and we propose that syndecan-2 plays a role as a co-receptor for this cytokine.

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Section: Fig 4 Co-immunoprecipitation Of Gmr␣ and Syndecan-2supporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Syndecan-2 Is Involved in the Mitogenic Activity and Signaling of Granulocyte-Macrophage Colony-stimulating Factor in Osteoblasts

Modrowski¹,

Basle²,

Lomri³

et al. 2000

Journal of Biological Chemistry

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“…Conversely, however, GM-CSF seems to limit the formation of the more mature, multinucleated osteoclasts (33,65,66,76). Since osteoblasts can also be stimulated to secrete GM-CSF (21,32,51,80), it is also possible that osteoblast-derived GM-CSF contributes to the regulation of osteoclastogenesis.…”

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confidence: 99%

Induction of Colony-Stimulating Factor Expression followingStaphylococcusorSalmonellaInteraction with Mouse or Human Osteoblasts

et al. 2000

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Staphylococcus aureus and Salmonella spp. are common causes of bone diseases; however, the immune response during such infections is not well understood. Colony-stimulating factors (CSF) have a profound influence on osteoclastogenesis, as well as the development of immune responses following infection. Therefore, we questioned whether interaction of osteoblasts with two very different bacterial pathogens could affect CSF expression by these cells. Cultured mouse and human osteoblasts were exposed to various numbers of S. aureus or Salmonella dublin bacteria, and a comprehensive analysis of granulocyte-macrophage (GM)-CSF, granulocyte (G)-CSF, macrophage (M)-CSF, and interleukin-3 (IL-3) mRNA expression and cytokine secretion was performed. Expression of M-CSF and IL-3 mRNAs by mouse osteoblasts was constitutive and did not increase significantly following bacterial exposure. In contrast, GM-CSF and G-CSF mRNA expression by mouse osteoblasts was dramatically upregulated following interaction with either viable S. aureus or Salmonella. This increased mRNA expression also translated into high levels of GM-CSF and G-CSF secretion by mouse and human osteoblasts following bacterial exposure. Viable S. aureus and Salmonella induced maximal levels of CSF mRNA expression and cytokine secretion compared to UV-killed bacteria. Furthermore, GM-CSF and G-CSF mRNA expression could be induced in unexposed osteoblasts separated by a permeable Transwell membrane from bacterially exposed osteoblasts. M-CSF secretion was increased in cultures of exposed human osteoblasts but not in exposed mouse osteoblast cultures. Together, these studies are the first to define CSF expression and suggest that, following bacterial exposure, osteoblasts may influence osteoclastogenesis, as well as the development of an immune response, via the production of these cytokines.

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“…[11] Increased GM-CSF also induces dose-related increases in the proliferation rate of human osteoblasts. [12] IL-18 can inhibit osteoclastogenesis by increasing osteoprotegerin in stromal or osteoblastic cells. [10] In addition to its physiological interactions with osteogenic cells, IL-18 also plays a role in pathological processes.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between IL-18 and Bone Metastasis in Female Breast Cancer

Nayır¹

2016

TJ Oncol

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OBJECTIVEBreast cancer is a metastatic disease that frequently (in approximately 70% of cases) affects the skeletal system. The aim of the present study was to compare serum IL-18 levels in breast cancer patients with and without bone metastases with healthy controls. METHODSIncluded were a total of 154 female breast cancer patients with bone metastases (n=53; Group 2) and without bone metastases (n=51; Group 1), as well as 50 healthy control subjects (Group 3). Serum IL-18 levels were compared among the groups. RESULTSMean serum IL-18 levels were significantly different between Groups 1 and 3 (p<0.001), Groups 2 and 3 (p<0.001), and Groups 2 and 1 (p=0.020). In receiver operating characteristic (ROC) curve analysis performed between Groups 1 and 2, sensitivity of serum IL-18 levels in patients with bone metastases was nearly 26 percent. CONCLUSIONLower rates of IL-18 sensitivity were detected in breast cancer patients with bone metastasis.

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Endogenous GM-CSF is involved as an autocrine growth factor for human osteoblastic cells

Cited by 25 publications

References 31 publications

Syndecan-2 Is Involved in the Mitogenic Activity and Signaling of Granulocyte-Macrophage Colony-stimulating Factor in Osteoblasts

Syndecan-2 Is Involved in the Mitogenic Activity and Signaling of Granulocyte-Macrophage Colony-stimulating Factor in Osteoblasts

Induction of Colony-Stimulating Factor Expression followingStaphylococcusorSalmonellaInteraction with Mouse or Human Osteoblasts

Relationship Between IL-18 and Bone Metastasis in Female Breast Cancer

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