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 up-regulation 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 bFGF 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.

Mesenchymal progenitors aging highlights a mir-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis / Candini, Olivia; Spano, Maria 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. - In: STEM CELLS. - ISSN 1066-5099. - STAMPA. - 33:3(2015), pp. 939-950. [10.1002/stem.1897]

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