Macrophage-Associated Osteoactivin/GPNMB Mediates Mesenchymal Stem Cell Survival, Proliferation, and Migration Via a CD44-Dependent Mechanism.

Title

Macrophage-Associated Osteoactivin/GPNMB Mediates Mesenchymal Stem Cell Survival, Proliferation, and Migration Via a CD44-Dependent Mechanism.

Creator

Yu Bing; Sondag Gregory R; Malcuit Christopher; Kim Min-Ho; Safadi Fayez F

Publisher

Journal of cellular biochemistry

Date

2016
2016-07

Description

Although MSCs have been widely recognized to have therapeutic potential in the repair of injured or diseased tissues, it remains unclear how functional activities of mesenchymal stem cells (MSCs) are influenced by the surrounding inflammatory milieu at the site of tissue injury. Macrophages constitute an essential component of innate immunity and have been shown to exhibit a phenotypic plasticity in response to various stimuli, which play a central role in both acute inflammation and wound repair. Osteoactivin (OA)/Glycoprotein non-metastatic melanoma protein B (GPNMB), a transmembrane glycoprotein that plays a role in cell differentiation, survival, and angiogenesis. The objective of this study was to investigate the potential role of OA/GPNMB in macrophage-induced MSC function. We found that reparative M2 macrophages express significantly greater levels of OA/GPNMB than pro-inflammatory M1 macrophages. Furthermore, using loss of function and rescue studies, we demonstrated that M2 macrophages-secreted OA/GPNMB positively regulates the viability, proliferation, and migration of MSCs. More importantly, we demonstrated that OA/GPNMB acts through ERK and AKT signaling pathways in MSCs via CD44, to induce these effects. Taken together, our results provide pivotal insight into the mechanism by which OA/GPNMB contributes to the tissue reparative phenotype of M2 macrophages and positively regulates functional activities of MSCs. J. Cell. Biochem. 117:

Subject

*CD44; *M2 MACROPHAGES; *MSC; *OA/GPNMB; Animals; Cell Movement/*physiology; Cell Proliferation/*physiology; Cell Survival/physiology; Eye Proteins/genetics/*metabolism; Hyaluronan Receptors/genetics/*metabolism; Knockout; Macrophages/cytology/*metabolism; MAP Kinase Signaling System/physiology; Membrane Glycoproteins/genetics/*metabolism; Mesenchymal Stem Cells/cytology/*metabolism; Mice

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1511–1521

Issue

7

Volume

117

Citation

Yu Bing; Sondag Gregory R; Malcuit Christopher; Kim Min-Ho; Safadi Fayez F, “Macrophage-Associated Osteoactivin/GPNMB Mediates Mesenchymal Stem Cell Survival, Proliferation, and Migration Via a CD44-Dependent Mechanism.,” NEOMED Bibliography Database, accessed November 27, 2021, https://neomed.omeka.net/items/show/3037.

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