Mesenchymal progenitors aging highlights a miR-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis.

Olivia Candini, Carlotta Spano, Alba Murgia, Giulia Grisendi, Elena Veronesi, Maria Serena Piccinno, Manuela Ferracin, Massimo Negrini, Francesca Giacobbi, Franco Bambi, Edwin Mark Horwitz, Pierfranco Conte, Paolo Paolucci, Massimo Dominici

Index: Stem Cells 33(3) , 939-50, (2015)

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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.© 2014 AlphaMed Press.