Enhanced Functional Response to CXCL12/SDF-1 Through Retroviral Overexpression of CXCR4 on M07e Cells: Implications for Hematopoietic Stem Cell Transplantation

Porecha, Nehal K.; English, Kyle; Hangoc, Giao; Broxmeyer, Hal E.; Christopherson, Kent W.

doi:10.1089/scd.2006.15.325

Cited by 20 publications

(15 citation statements)

References 29 publications

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“…Interestingly, myogenin levels further declined in C2C12 cells that overexpressed CXCR4. We consider this finding as an indication that, like previously reported for several other cell types (Ödemis et al, 2002;Porecha et al, 2006;Ehtesham et al, 2006), the response of myogenic progenitors/myoblasts to SDF1 is additionally controlled by CXCR4 (cell surface) expression levels. Although data on SDF1 concentrations present in the limb bud are at present unavailable, SDF1 concentrations of у1 ng/ml, which were found by us to affect myogenesis, could -during development -well be reached locally.…”

Section: Discussionsupporting

confidence: 83%

The chemokine SDF1 controls multiple steps of myogenesis through atypical PKCζ

Ödemis

Boosmann

Dieterlen

et al. 2007

Journal of Cell Science

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Mice deficient in the SDF1-chemokine-receptor CXCR4, exhibit severe defects of secondary limb myogenesis. To further elucidate the role of SDF1 in muscle development, we have now analyzed putative effects of this chemokine on proliferation, migration and myogenic differentiation of mouse C2C12 myogenic progenitor/myoblast cells. In addition, we have characterized the signaling pathways employed by SDF1-CXCR4 to control myogenesis. We found that SDF1 stimulates proliferation and induces migration of C2C12 cells with a potency similar to that of FGF2 and HGF, which both represent prototypical extracellular regulators of myogenesis. In addition, SDF1 inhibits myogenic differentiation in both C2C12 cells and primary myoblasts, as assessed by MyoD, myosin heavy chain and/or myogenin expression. Regarding signaling pathways, C2C12 cells responded to SDF1 with activation (phosphorylation) of Erk and PKCζ, whereas even after prolonged SDF1 treatment for up to 120 minutes, levels of activated Akt, p38 and PKCα or PKCβ remained unaffected. Preventing activation of the classic MAP kinase cascade with the Erk inhibitor UO126 abolished SDF1-induced proliferation and migration of C2C12 cells but not the inhibitory action of SDF1 on myogenic differentiation. Moreover, the effects of SDF1 on proliferation, migration and differentiation of C2C12 cells were all abrogated in the presence of myristoylated PKCζ peptide pseudosubstrate and/or upon cellular depletion of PKCζ by RNA interference. In conclusion, our findings unravel a previously unknown role of CXCR4-PKCζ signaling in myogenesis. The potent inhibitory effects of SDF1 on myogenic differentiation point to a major function of CXCR4-PKCζ signaling in the control of secondary muscle growth.

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Section: Discussionsupporting

confidence: 83%

The chemokine SDF1 controls multiple steps of myogenesis through atypical PKCζ

Ödemis

Boosmann

Dieterlen

et al. 2007

Journal of Cell Science

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“…Such survivalpromoting activity has also been confirmed in vivo, wherein, in combination with other cytokines, SDF-1 increases the long-term survival of lethally irradiated mice [84]. Supporting this notion, retroviral-mediated CXCR4 overexpression in M07e cells have resulted in significantly increased cell survival [70]. In apparent agreement with these studies, SDF-1/CXCR4 signaling has been shown to promote HSPC proliferation under certain experimental conditions.…”

supporting

confidence: 57%

“…Consistent with these results, CXCR4 overexpression on human cord blood and MPB-derived CD34 + cells has resulted in significantly enhanced chemotaxis toward SDF-1 in vitro as well as their enhanced BM engraftment in NOD/SCID recipient mouse [67][68][69]. Similarly, retroviral-mediated CXCR4 overexpression on M07e cells (an established model of human HPCs) resulted in significantly increased SDF-1 chemotaxis and cell survival [70]. Taken together, these results delineate the significant role of SDF-1/CXCR4 axis in the homing and engraftment of HSPCs to BM.…”

Section: Sdf-1/cxcr4 Signaling: a Key Regulator Of Homing And Engraftmentioning

confidence: 61%

Stromal-Derived Factor-1/CXCR4Signaling: Indispensable Role in Homing and Engraftment of Hematopoietic Stem Cells in Bone Marrow

Sharma

Afrin

Satija

et al. 2011

Stem Cells and Development

117

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Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) in bone marrow is the major determining factor in success of hematopoietic stem cell transplantation. This is a complex, multistep process orchestrated by the coordinated interplay between adhesion molecules, cytokines, growth factors, and regulatory cofactors, many of which remain to be defined. Recent studies have highlighted the pivotal role of unique stromal-derived factor-1 (SDF-1)/CXCR4 signaling in the regulation of HSPC homing and subsequent engraftment. In addition, studies suggest that SDF-1/CXCR4 signaling acts as an essential survival-promoting factor of transplanted HSPCs as well as maintenance of quiescent HSCs in bone marrow niche. These pleiotropic effects exerted by SDF-1/CXCR4 axis make this unique signaling initiator very promising, not only for optimal hematopoietic reconstitution but also for the development of innovative approaches to achieve restoration, regeneration, or repair of other damaged tissues potentially amendable to reversal by stem cell transplantation. This goal can only be achieved when the role of SDF-1/CXCR4 axis in hematopoietic transplantation is clearly defined. Hence, this review presents current knowledge of the mechanisms through which SDF-1/CXCR4 signaling promotes restoration of hematopoiesis by regulating the homing and engraftment of HSPCs.

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“…In the mobilizing process, as we observed in this study by ELISA (Fig. 3B), a transient increase of SDF-1· in BM is followed by its proteolytic degradation and the level of CXCR4 expression increase on the surface of stem cells are essential mechanisms (21,22).…”

Section: Discussionsupporting

confidence: 69%

Osteoclast activation by receptor activator of NF-κB ligand enhances the mobilization of hematopoietic progenitor cells from the bone marrow in acute injury

Cho

Joo²,

Han

et al. 2010

Int J Mol Med

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Abstract. Osteoclasts (OCLs) are multinucleated cells that are derived from the monocyte/macrophage hematopoietic lineage in response to receptor activator of NF-κB ligand (RANKL) activation. They are specialized cells responsible for physiological bone resorption and as well as pathologic bone loss. In addition to their unique ability to resorb bone, OCLs also play a potential role in the mobilization of hematopoietic progenitor cells from the bone marrow (BM), particularly under various stress stimuli (e.g. hypoxia, injury or inflammation). We investigated the effect of activated OCLs on the stem cell niche and whether this leads to mobiliz-ation of hematopoietic progenitors. We induced activated OCLs from the RAW264.7 cell line through stimulation with RANKL and we quantified the levels of the stem cell niche component SDF-1 on the osteblasts and CXCR4 on the bone marrow cells (BMCs) by culturing with supernatants from activated OCLs. In addition, we exposed mice to stress by inducing liver injury with CCl 4 followed by injecting RANKL to activate OCLs and compared the effect on the mobilization of hematopoietic progenitor cells from the BM. We found that functional OCLs cleaved SDF-1· in the osteoblasts and increased CXCR4 expression in the BMCs. Moreover, under stress in vivo, mobilized hematopoietic progenitor cells were significantly increased after RANKL treatment. These results suggest that OCLs might be involved in alteration of the interaction between SDF-1 and CXCR4 leading to mobilization of hematopoietic progenitor cells from the BM.

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Enhanced Functional Response to CXCL12/SDF-1 Through Retroviral Overexpression of CXCR4 on M07e Cells: Implications for Hematopoietic Stem Cell Transplantation

Cited by 20 publications

References 29 publications

The chemokine SDF1 controls multiple steps of myogenesis through atypical PKCζ

The chemokine SDF1 controls multiple steps of myogenesis through atypical PKCζ

Stromal-Derived Factor-1/CXCR4Signaling: Indispensable Role in Homing and Engraftment of Hematopoietic Stem Cells in Bone Marrow

Osteoclast activation by receptor activator of NF-κB ligand enhances the mobilization of hematopoietic progenitor cells from the bone marrow in acute injury

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