IGF2 modulates the microenvironment for osteoclastogenesis

Nakao, Kimihisa; Aoyama, Mineyoshi; Fukuoka, Hayato; Fujita, Masataka; Miyazawa, Ken; Asai, Kiyofumi; Goto, Shigemi

doi:10.1016/j.bbrc.2008.11.083

Cited by 30 publications

(20 citation statements)

References 24 publications

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“…The upregulation of IGF-2 derived from nonosteoclastic cells may be a crucial factor for osteoclast differentiation. (52) Furthermore, it has been reported that the local production of IGF-2 may modulate both osteoblast-osteoclast interactions and osteoclast formation and may play an important role in bone remodeling. (52) It has been reported recently that IGF-1 and BMP-2 can act synergistically in promoting chondrogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…(52) Furthermore, it has been reported that the local production of IGF-2 may modulate both osteoblast-osteoclast interactions and osteoclast formation and may play an important role in bone remodeling. (52) It has been reported recently that IGF-1 and BMP-2 can act synergistically in promoting chondrogenesis. (53,54) However, the molecular mechanisms of the IGF-2 stimulation that enhance osteoclast formation remain unknown.…”

Section: Discussionmentioning

confidence: 99%

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Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation

Chen

Jiang

Huang

et al. 2010

Journal of Bone and Mineral Research

223

245

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Efficient osteogenic differentiation and bone formation from mesenchymal stem cells (MSCs) should have clinical applications in treating nonunion fracture healing. MSCs are adherent bone marrow stromal cells that can self-renew and differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. We have identified bone morphogenetic protein 9 (BMP-9) as one of the most osteogenic BMPs. Here we investigate the effect of insulin-like growth factor 2 (IGF-2) on BMP-9-induced bone formation. We have found that endogenous IGF-2 expression is low in MSCs. Expression of IGF-2 can potentiate BMP-9-induced early osteogenic marker alkaline phosphatase (ALP) activity and the expression of later markers. IGF-2 has been shown to augment BMP-9-induced ectopic bone formation in the stem cell implantation assay. In perinatal limb explant culture assay, IGF-2 enhances BMP-9-induced endochondral ossification, whereas IGF-2 itself can promote the expansion of the hypertropic chondrocyte zone of the cultured limb explants. Expression of the IGF antagonists IGFBP3 and IGFBP4 leads to inhibition of the IGF-2 effect on BMP-9-induced ALP activity and matrix mineralization. Mechanistically, IGF-2 is further shown to enhance the BMP-9-induced BMPR-Smad reporter activity and Smad1/5/8 nuclear translocation. PI3-kinase (PI3K) inhibitor LY294002 abolishes the IGF-2 potentiation effect on BMP-9-mediated osteogenic signaling and can directly inhibit BMP-9 activity. These results demonstrate that BMP-9 crosstalks with IGF-2 through PI3K/AKT signaling pathway during osteogenic differentiation of MSCs. Taken together, our findings suggest that a combination of BMP-9 and IGF-2 may be explored as an effective bone-regeneration agent to treat large segmental bony defects, nonunion fracture, and/or osteoporotic fracture. © 2010 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation

Chen

Jiang

Huang

et al. 2010

Journal of Bone and Mineral Research

223

245

View full text Add to dashboard Cite

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“…The derived average difference value (AD) was globally normalized and targeted to all probe sets equal to 100 before comparative analysis. To examine the expression differences of each gene, we performed comparison analysis using the GenePix pro software (Axon Instruments), and only genes (probe sets) showing greater than twofold changes were chosen ( P < 0.001), as described previously (Fukuoka et al, 2005; Nakao et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

Update and external validation of a head and neck cancer prognostic model

et al. 2012

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“…Increased synthesis was found in intestinal epithelial cells from patients with ulcerative colitis, and matrix metalloproteinases from lamina propria myofibroblasts were found to act as proteolytic activators of the chemokine [110]. A novel role for CXCL7 in metabolism of the bone was recently established by showing that hypoxic stress (i.e., IGF2-mediated giant osteoclast formation) is promoted by stromal bone marrow cell-secreted CXCL7 and becomes enhanced by CXCL12 from osteoblastic cells [111]. Concerning CXCL4 both the original chemokine and its variant CXCL4L1 have not only been found in platelets, monocytes and T cells, but are also expressed in human microvascular ECs, in human aortic as well as coronary smooth muscle cells, and a human colonic epithelial cell line [112].…”

Section: Expression Of Platelet Chemokines By Other Cell Typesmentioning

confidence: 99%

Platelet-derived chemokines: pathophysiology and therapeutic aspects

Flad

Brandt

2010

Cell. Mol. Life Sci.

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The identification of chemokines in blood platelets has strengthened our view of these cells as participants in immune host defense. Platelet chemokines representing prestored and rapidly releasable proteins may play a major role as first-line inflammatory mediators. This is evident from their capability to recruit early inflammatory cells such as neutrophil granulocytes and monocytes and even to exhibit direct antimicrobial activity. However, insight is growing that platelet chemokines may be also long-term regulators, e.g., by activating T lymphocytes, by modulating the formation of endothelium and even thrombocytopoiesis itself. This review deals with the individual and cooperative functionality of platelet chemokines, as well as their potential as a basis for therapeutic intervention in the pathology of inflammation, infection, allergy and tumors. Within this context, therapeutic strategies based on the use of antibodies, modified chemokines, chemokine-binding proteins and chemokine receptor antagonists as well as first clinical studies will be addressed.

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IGF2 modulates the microenvironment for osteoclastogenesis

Cited by 30 publications

References 24 publications

Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation

Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation

Update and external validation of a head and neck cancer prognostic model

Platelet-derived chemokines: pathophysiology and therapeutic aspects

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