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作者:Agnieszka Stokowskia,b,c, Songtao Shid, Tao Sunc, Peter Mark Bartolde, Simon Andrea Koblara,b, Stan Gronthosc作者单位:aAustralian Research Council, Centre for Molecular Genetics of Development,bSchool of Molecular and Biomedical Science (Genetics), andeColgate Australian Clinical Dental Research Centre, Dental School, University of Adelaide, Adelaide, South Australia, Australia;cMesenchymal Stem Cell Group, Divisio ! h! A4 ~+ M% c1 }0 j
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【摘要】
7 D. ^# v7 A3 d# A/ ?; W/ a! z E- R Human adult dental pulp stem cells (DPSCs) reside predominantly within the perivascular niche of dental pulp and are thought to originate from migrating neural crest cells during development. The Eph family of receptor tyrosine kinases and their ligands, the ephrin molecules, play an essential role in the migration of neural crest cells during development and stem cell niche maintenance. The present study examined the expression and function of the B-subclass Eph/ephrin molecules on DPSCs. Multiple receptors were primarily identified on DPSCs within the perivascular niche, whereas ephrin-B1 and ephrin-B3 were expressed by the surrounding pulp tissue. EphB/ephrin-B bidirectional signaling inhibited cell attachment and spreading, predominately via the mitogen-activated protein kinase (MAPK) pathway for forward signaling and phosphorylation of Src family tyrosine kinases via reverse ephrin-B signaling. DPSC migration was restricted through unidirectional ephrin-B1-activated EphB forward signaling, primarily signaling through the MAPK pathway. Furthermore, we observed that ephrin-B1 was downregulated in diseased adult teeth compared with paired uninjured controls. Collectively, these studies suggest that EphB/ephrin-B molecules play a role in restricting DPSC attachment and migration to maintain DPSCs within their stem cell niche under steady-state conditions. These results may have implications for dental pulp development and regeneration.
3 z: v7 f* ~; M' ?6 X 【关键词】 Eph Ephrin MSC Dental pulp stem cell Migration Adhesion Spreading/ M# x7 \$ T, K+ `9 t2 O
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