Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors: Implications for low bone mass phenotype
Copyright policy )Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors: Implications for low bone mass phenotype
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.
- Indiana University School of Medicine United States
- NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES Japan
- National Institutes for Quantum and Radiological Science and Technology Japan
- Indiana University United States
Adenosine Triphosphatases, Male, Osteoblasts, RecQ Helicases, Stem Cells, DNA Helicases, Down-Regulation, Gene Expression Regulation, Developmental, Cell Differentiation, Haploidy, Alkaline Phosphatase, Osteocytes, Bone and Bones, Mice, Phenotype, Bone Density, Animals, Stromal Cells, Cells, Cultured
Adenosine Triphosphatases, Male, Osteoblasts, RecQ Helicases, Stem Cells, DNA Helicases, Down-Regulation, Gene Expression Regulation, Developmental, Cell Differentiation, Haploidy, Alkaline Phosphatase, Osteocytes, Bone and Bones, Mice, Phenotype, Bone Density, Animals, Stromal Cells, Cells, Cultured
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