title: Mesenchymal progenitors aging highlights a miR-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis.
abstract: Human aging is associated with a decrease in tissue functions combined with a decline in stem cells frequency and activity followed by a loss of regenerative capacity. The molecular mechanisms behind this senescence remain largely obscure, precluding targeted approaches to counteract aging. Focusing on mesenchymal stromal/stem cells (MSC) as known adult progenitors, we identified a specific switch in miRNA expression during aging, revealing a miR-196a upregulation which was inversely correlated with MSC proliferation through HOXB7 targeting. A forced HOXB7 expression was associated with an improved cell growth, a reduction of senescence, and an improved osteogenesis linked to a dramatic increase of autocrine basic fibroblast growth factor secretion. These findings, along with the progressive decrease of HOXB7 levels observed during skeletal aging in mice, indicate HOXB7 as a master factor driving progenitors behavior lifetime, providing a better understanding of bone senescence and leading to an optimization of MSC performance.
authors.affiliation: Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Olivia
authors.initials: O
authors.lastname: Candini
authors.forename: Carlotta
authors.initials: C
authors.lastname: Spano
authors.forename: Alba
authors.initials: A
authors.lastname: Murgia
authors.forename: Giulia
authors.initials: G
authors.lastname: Grisendi
authors.forename: Elena
authors.initials: E
authors.lastname: Veronesi
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Piccinno
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Giacobbi
authors.forename: Franco
authors.initials: F
authors.lastname: Bambi
authors.forename: Edwin Mark
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Conte
authors.forename: Paolo
authors.initials: P
authors.lastname: Paolucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010012:Osteogenesis
chemical_list: C490538:HOXB7 protein, human; D018398:Homeodomain Proteins; C093253:Hoxb7 protein, mouse; C542543:MIRN196 microRNA, human; C000602251:MIRN196 microRNA, mouse; D035683:MicroRNAs
keywords: Aging; Bone; Bone marrow stromal cells; Homeobox genes