Osteopontin activates mesenchymal stem cells to repair skin wound.

Wenping Wang,Pei Li,Junzi Jiang,Shirong Li,Yanyan Cui,Zhenxiang Wang,Wei Li,Robert W Dettman

doi:10.1371/journal.pone.0185346

Abstract

Mesenchymal stem cells (MSCs) are promising candidates for skin wound repair due to their capabilities of accumulating at wounds and differentiating into multiple types of skin cells. However, the underlying mechanisms responsible for these processes remain unclear. In this study, we found that osteopontin (OPN) stimulated the migration of MSCs in vitro, and observed the recruitment of endogenous MSCs to a skin wound and their differentiation into keratinocytes and endothelial cells. In OPN knock-out mice, the recruitment of MSCs to the skin wound was significantly inhibited, and wound closure was hampered after an intradermal injection of exogenous MSCs compared to wild-type mice. Consistent with these observations, the expressions of adhesion molecule CD44 and its receptor E-selectin were significantly decreased in the lesions of OPN knock-out mice compared with wild-type mice suggesting that OPN may regulate the migration of MSCs through its interactions with CD44 during skin wound recovery. In summary, our data demonstrated that OPN played a critical role in activating the migration of MSCs to injured sites and their differentiation into specific skin cell types during skin wound healing.

Highlights

Skin wound healing is a multi-stage process that orchestrates the reconstruction of dermal and epidermal layers
A previous study found that OPN expression was significantly up-regulated during wound healing, but little is known about its mechanisms[27]This paper shows that the expression of osteopontin increases in wounds, facilitating the mobilization of bone marrow derived stem cells into wounds by interacting with CD44
We showed that OPN promoted the activation of Mesenchymal stem cells (MSCs), including their migration and specific cell differentiation during skin wound healing and in vitro

Summary

Introduction

Skin wound healing is a multi-stage process that orchestrates the reconstruction of dermal and epidermal layers. This process involves three overlapping phases, including the inflammatory, proliferation, and remodeling phases. Mesenchymal stem cells (MSCs) can differentiate into a variety of cell types, including osteoblasts, chondrocytes, adipocytes, myoblasts[1] endothelial cells[2, 3], keratinocytes[2] neural cells[4, 5], and hepatocytes[6, 7] in vitro. MSCs can differentiate into tissue-specific cells in response to cues provided by different organs[8] MSCs could differentiate to endothelial cells, myofibroblasts and pericytes cells, promoting wound healing in vivo[2]. MSCs have been used in clinical trials[11, 12]for the successful treatment of chronic wounds[13] MSCs are reported to be involved in all three phases[14,15,16]of skin wound healing

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Conclusion