The cellular and molecular mechanisms that underlie skeletal abnormalities in defective Recq14-related syndromes are poorly understood. Our objective in this study was to explore the function of Recq14 in osteoblast biology both in vitro and in vivo. Immunohistochemistry on adult mouse bone showed Recq14 protein localization in active osteoblasts around growth plate, but not in fully differentiated osteocytes. Consistent with this finding, Recq14 gene expression was high in proliferating mouse osteoblastic MC3T3.E1 cells and decreased as cells progressively lost their proliferation activity during differentiation. Recq14 overexpression in osteoblastic cells exhibited higher proliferation activity, while its depletion impeded cell growth. In addition, bone marrow stromal cells from male Recq14+/- mice had fewer progenitor cells, including osteoprogenitors, indicated by reduced total fibroblast colony forming units (CFU-f) and alkaline phosphatase-positive CFU-f colonies concomitant with reduced bone mass. These findings provide evidence that Recq14 functions as a regulatory protein during osteoprogenitor proliferation, a critical cellular event during skeleton development. (c) 2006 Elsevier Inc. All rights reserved.