Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells.
Bottom Line: However, cADPR had no effect on adipogenesis or osteogenesis in human MSCs.Our results indicate that cADPR is a novel regulator of Ca(2+) (i) oscillations in human MSCs.It permeates the cell membrane through the nucleoside transporters and increases Ca(2+) oscillation via activation of the TRPM2 channel, resulting in enhanced phosphorylation of ERK1/2 and, thereby, stimulation of human MSC proliferation.
Affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.Show MeSH
Mentions: Previous studies have demonstrated that concentrative nucleoside transporters (CNTs) and equilibrative nucleoside transporters (ENTs) are responsible for the transport of external cADPR into human haematopoietic progenitors  and human promyelocytic leukemia (HL)-60 cells . To determine whether these nucleoside transporters are present in human MSCs, the related mRNAs were examined by RT-PCR, which showed significant expression of ENT1/ENT2 and CNT1/CNT3 in the cells (Fig. 3A). Two other components of the cADPR-pathway were also present in human MSCs, the hexameric hemichannel connexin 43 (Cx43) and the bone marrow stromal cell antigen-1 (BST-1). Cx43 has been demonstrated to mediate the nicotinamide adenine dinucleotide (NAD+) transport and it is known to be functionally interacting with the multifunctional ecto-enzymes, CD38 and/or BST-1 (also called CD157) in the plasma membrane, both catalyse the synthesis and hydrolysis of cADPR . Indeed, BST-1 (CD157) [38, 39], but not CD38, was strongly expressed in human MSCs (Fig. 3A).
Affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.