Sphingosine 1-Phosphate Receptor 1 Is Required for MMP-2 Function in Bone Marrow Mesenchymal Stromal Cells: Implications for Cytoskeleton Assembly and Proliferation

• Published in: Stem cells international 2018-01, Vol.2018 (2018), p.1-18
• Main Authors: Zecchi-Orlandini, Sandra, Meacci, E., Nosi, Daniele, Vestri, Ambra, Matteini, Francesca, Chellini, Flaminia, Frati, Alessia, Tani, Alessia, Pierucci, Federica, Sassoli, Chiara, Anderloni, Giulia
• Format: Article
• Language: English
• Subjects: Actin; Assembly; Autocrine signalling; Bone marrow; Cell proliferation; Clinical trials; Cytoskeleton; Extracellular matrix; Fibers; Fingolimod; Gelatinase A; Gene expression; Health aspects; Hypoxia; Kinases; Lamellipodia; Matrix metalloproteinase; Mesenchymal stem cells; Mesenchyme; Metalloproteinase; Paracrine signalling; Pharmacology; Phosphates; Physiology; Pseudopodia; Regenerative medicine; Regulators; Secretion; Sphingosine 1-phosphate; Stem cells; Stromal cells; Tissue engineering; Vinculin
• ISSN: 1687-966X; 1687-9678; 1687-9678
• DOI: 10.1155/2018/5034679

Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked. Notably, active S1PR1/MMP-2 signalling is required for F-actin structure assembly (lamellipodia, microspikes, and stress fibers) and, in turn, cell proliferation. Moreover, in experimental conditions resembling the damaged/regenerating tissue microenvironment (hypoxia), S1P/S1PR1 system is also required for HIF-1α expression and vinculin reduction. Our findings demonstrate for the first time the trophic role of S1P/S1PR1 signalling in maintaining BM-MSCs’ ability to modulate MMP-2 function, necessary for cytoskeleton reorganization and cell proliferation in both normoxia and hypoxia. Altogether, these data provide new perspectives for considering S1P/S1PR1 signalling a pharmacological target to preserve BM-MSC properties and to potentiate their beneficial potential in tissue repair.