Open AccessMesenchymal Progenitors Aging Highlights a mi R ‐196 Switch Targeting HOXB7 as Master Regulator of Proliferation and Osteogenesis
Author(s) -
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
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1897
Subject(s) - mesenchymal stem cell , biology , senescence , progenitor cell , stem cell , microbiology and biotechnology , autocrine signalling , stromal cell , downregulation and upregulation , cancer research , immunology , cell culture , genetics , gene
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. S tem C ells 2015;33:939–950