title: Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors: Implications for low bone mass phenotype.
abstract: 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.
authors.affiliation: Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jieping
authors.initials: J
authors.lastname: Yang
authors.forename: Sreemala
authors.initials: S
authors.lastname: Murthy
authors.forename: Therry
authors.initials: T
authors.lastname: Winata
authors.forename: Sean
authors.initials: S
authors.lastname: Werner
authors.forename: Masumi
authors.initials: M
authors.lastname: Abe
authors.forename: Agasanur K
authors.initials: AK
authors.lastname: Prahalad
authors.forename: Janet M
authors.initials: JM
authors.lastname: Hock
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000166:cytology / Q000201:enzymology; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004265:DNA Helicases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006238:Haploidy; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000201:enzymology; D010011:Osteocytes / Q000166:cytology / Q000201:enzymology; D010641:Phenotype; D053484:RecQ Helicases; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology
chemical_list: D000469:Alkaline Phosphatase; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D053484:RecQ Helicases