Interleukin-11 Induces Osteoblast Differentiation and Acts Synergistically with Bone Morphogenetic Protein-2 in C3H10T1/2 Cells

Suga, Kazutaka; Saitoh, Minori; Fukushima, Shinji; Takahashi, Kohichiro; Nara, Hiromi; Yasuda, Shuhei; Miyata, Keiji

doi:10.1089/107999001753124435

Cited by 48 publications

(33 citation statements)

References 53 publications

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“…Other genes found overexpressed in B02 cells (Table 1) include proteoglycan 1 (PRG1), a gene catalogued in the Skeletal Gene Database [40]; interleukin 11 (IL11), a cytokine reported to enhance osteoblast differentiation of mouse mesenchymal progenitors [41] and to act synergically with BMP-2 [42]; and follistatin (FST) that is expressed by chondrocytes and osteoblasts and acts as a local regulator of BMPs function in skeletal cells [43,44]. CTGF, PRG1, IL11 and FST regulation observed in B02 cells is coherent with a previous microarray study [14] that showed an overexpression of these genes in highly bone metastatic MDA-MB-231 subpopulations.…”

Section: Resultsmentioning

confidence: 99%

Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells

Bellahcène

Bachelier

Detry

et al. 2006

Breast Cancer Res Treat

102

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Metastatic breast cancer cells exhibit the selective ability to seed and grow in the skeleton. We and others have previously reported that human breast tumors which metastasize to the skeleton overexpress bone matrix extracellular proteins. In an attempt to reveal the osteoblast-like phenotype of osteotropic breast cancer cells, we performed a microarray study on a model of breast cancer bone metastasis consisting of the MDA-MB-231 human cell line and its variant B02 selected for its high capacity to form bone metastases in vivo. Analysis of B02 cells transcriptional profile revealed that 11 and 9 out of the 50 most up- and down-regulated mRNAs, respectively, corresponded to genes which expression has been previously associated with osteoblastic differentiation process. Thus, osteoblast specific cadherin 11 which mediates the differentiation of mesenchymal cells into osteoblastic cells is up-regulated in B02. While S100A4, recently described as a key negative regulator of osteoblast differentiation, is the most down-regulated gene in B02 cells. RT-PCR and western blotting experiments allowed the validation of the modulation of several genes of interest. Using immunohistochemistry, performed on human breast primary tumors and their matched liver and bone metastases, we were able to confirm that the osteoblast-like pattern of gene expression observed in our model holds true in vivo. This is the first report demonstrating a gene-expression pattern corresponding to the acquisition of an osteomimetic phenotype by bone metastatic breast cancer cells.

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Section: Resultsmentioning

confidence: 99%

Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells

Bellahcène

Bachelier

Detry

et al. 2006

Breast Cancer Res Treat

102

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“…142,143 In vitro, IL-11 enhances osteoclast formation and bone resorption, but also stimulates expression of osteoblastic markers in mesenchymal progenitor cells. [144][145][146] During osteogenesis, IL-11 synergizes with BMP-2 in a dose-dependent fashion to enhance the in vitro osteoblastic differentiation of progenitor cells. 146 Although the mechanical properties of the formed bone were not significantly different compared to BMP-2 alone, a similar synergistic increase in bone formation rate was seen after combined implantation of IL-11 and BMP-2 in a rat ectopic and rabbit segmental bone defect model.…”

Section: Cytokinesmentioning

confidence: 99%

“…[144][145][146] During osteogenesis, IL-11 synergizes with BMP-2 in a dose-dependent fashion to enhance the in vitro osteoblastic differentiation of progenitor cells. 146 Although the mechanical properties of the formed bone were not significantly different compared to BMP-2 alone, a similar synergistic increase in bone formation rate was seen after combined implantation of IL-11 and BMP-2 in a rat ectopic and rabbit segmental bone defect model. 147,148 Overall, these results show that IL-11 actions predominantly enhance BMP-2-induced bone formation.…”

Section: Cytokinesmentioning

confidence: 99%

Growth Factor Interactions in Bone Regeneration

Kempen

Creemers

Alblas

et al. 2010

Tissue Engineering Part B: Reviews

100

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Bone regeneration is a complex process regulated by a large number of bioactive molecules. Many growth factors and cytokines involved in the natural process of bone healing have been identified and tested as potential therapeutic candidates to enhance the regeneration process. Although many of these studies show an enhancement of the bone regeneration process by a single drug therapy, in vivo bone regeneration is the result of a complex interplay between the applied growth factor and various endogenous produced growth factors. To investigate these growth factor interactions, various studies have investigated the effect of growth factor combinations on bone regeneration. This review provides an overview of the growth factor and cytokine combinations tested in translational bone regeneration studies and shows that their interaction may result in an enhancement or inhibition of bone formation.

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“…IL-11 promotes the maturation of megakaryocytes in vitro (Bruno et al, 1991;Burstein et al, 1992;Teramura et al, 1992;Yonemura et al, 1992) and increases peripheral platelets in myelosuppressed animals (Neben et al, 1993;Yonemura et al, 1993;Nash et al, 1995;Schlerman et al, 1996). IL-11 induces osteoblast differentiation and acts synergistically with BMP-2 in C3H10T1/2 cells (Suga et al, 2001). IL-11 also acts synergistically with BMP-2 to accelerate bone formation in a rat ectopic model (Suga et al, 2003).…”

Section: Discussionmentioning

confidence: 99%