title: CCL5/RANTES is important for inducing osteogenesis of human mesenchymal stem cells and is regulated by dexamethasone.
abstract: In this study, we examine the effect of chemokine (C-C motif) ligand 5 (CCL5)/Regulated on Activation Normal T cell Expressed and Secreted (RANTES), a pro-inflammatory cytokine on osteogenic differentiation of human mesenchymal stem cells (hMSCs). We found CCL5 expression was increased during osteogenic differentiation of hMSCs and CCL5 expression is dependent on the presence of dexamethasone. Knocking down endogenous CCL5 expression blocked osteogenesis, as revealed by decreasing alkaline phosphatase (ALP) activity and a reduction in the expression levels of ALP, bone sialoprotein (BSP), and osteopontin (OPN). Of note, the overexpression of CCL5 was sufficient to increase ALP expression and activity. Moreover, the down-regulation of chemokine (C-C motif) receptor 1 (CCR1), one of the CCL5 receptors, significantly decreased the osteogenesis of hMSCs. Interestingly, the down-regulation of CCR1, but not CCL5, was sufficient to affect the cell numbers during the process of osteogenesis. Our findings reveal that both CCL5 and CCR1 are required for osteogenesis of human MSCs, CCL5 is sufficient for the osteogenesis, and provide a novel link between dexamethasone and CCL5 in human osteogenesis.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Liu
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Kao
authors.forename: Wei-Kai
authors.initials: WK
authors.lastname: Huang
authors.forename: Kun-Yi
authors.initials: KY
authors.lastname: Lin
authors.forename: Shinn-Chih
authors.initials: SC
authors.lastname: Wu
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hsu
authors.forename: Scott C
authors.initials: SC
authors.lastname: Schuyler
authors.forename: Long-Yuan
authors.initials: LY
authors.lastname: Li
authors.forename: Frank
authors.initials: F
authors.lastname: Leigh Lu
authors.forename: Jean
authors.initials: J
authors.lastname: Lu
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics
chemical_list: D018946:Chemokine CCL5; D003907:Dexamethasone