Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors: Implications for low bone mass phenotype

Journal Article · Fri May 26 00:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.03.104· OSTI ID:20798975

Jieping, Yang ^[1]; Murthy, Sreemala ^[1]; Winata, Therry ^[1]; Werner, Sean ^[1]; Abe, Masumi ^[2]; Prahalad, Agasanur K ^[1]; Hock, Janet M ^[1]

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1. Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN (United States)
2. National Institute of Radiological Sciences, Chiba (Japan)

The cellular and molecular mechanisms that underlie skeletal abnormalities in defective Recql4-related syndromes are poorly understood. Our objective in this study was to explore the function of Recql4 in osteoblast biology both in vitro and in vivo. Immunohistochemistry on adult mouse bone showed Recql4 protein localization in active osteoblasts around growth plate, but not in fully differentiated osteocytes. Consistent with this finding, Recql4 gene expression was high in proliferating mouse osteoblastic MC3T3.E1 cells and decreased as cells progressively lost their proliferation activity during differentiation. Recql4 overexpression in osteoblastic cells exhibited higher proliferation activity, while its depletion impeded cell growth. In addition, bone marrow stromal cells from male Recql4+/- 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 Recql4 functions as a regulatory protein during osteoprogenitor proliferation, a critical cellular event during skeleton development.

• OSTI ID: 20798975
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 344, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.03.104; PII: S0006-291X(06)00622-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALKALINE PHOSPHATASE
BIOLOGY
BONE CELLS
BONE MARROW
CELL PROLIFERATION
COLONY FORMING UNITS
FIBROBLASTS
GROWTH
IN VITRO
IN VIVO
MICE
PHENOTYPE
SKELETON