Mesenchymal Progenitors Aging Highlights a miR-196 Switch Targeting HOXB7 as Master Regulator of Proliferation and Osteogenesis. (17th February 2015)

• Record Type: Journal Article
• Authors: Candini, Olivia; Spano, Carlotta; Murgia, Alba; Grisendi, Giulia; Veronesi, Elena; Piccinno, Maria Serena; Ferracin, Manuela; Negrini, Massimo; Giacobbi, Francesca; Bambi, Franco; Horwitz, Edwin Mark; Conte, Pierfranco; Paolucci, Paolo; Dominici, Massimo
• Is Part Of: Stem cells. Volume 33:Number 3(2015:Mar.)
• Page Start: 939
• Page End: 950
• Publication Date: 2015-02-17
• Subjects: Bone marrow stromal cells -- Aging -- Homeobox genes -- Bone; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1897
• Languages: English
• ISSNs: 1066-5099

Abstract

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. Stem Cells 2015;33:939–950