title: Connective Tissue Growth Factor reporter mice label a subpopulation of mesenchymal progenitor cells that reside in the trabecular bone region.
abstract: Few gene markers selectively identify mesenchymal progenitor cells inside the bone marrow. We have investigated a cell population located in the mouse bone marrow labeled by Connective Tissue Growth Factor reporter expression (CTGF-EGFP). Bone marrow flushed from CTGF reporter mice yielded an EGFP+ stromal cell population. Interestingly, the percentage of stromal cells retaining CTGF reporter expression decreased with age in vivo and was half the frequency in females compared to males. In culture, CTGF reporter expression and endogenous CTGF expression marked the same cell types as those labeled using Twist2-Cre and Osterix-Cre fate mapping approaches, which previously had been shown to identify mesenchymal progenitors in vitro. Consistent with this past work, sorted CTGF+ cells displayed an ability to differentiate into osteoblasts, chondrocytes, and adipocytes in vitro and into osteoblast, adipocyte, and stromal cell lineages after transplantation into a parietal bone defect. In vivo examination of CTGF reporter expression in bone tissue sections revealed that it marked cells highly localized to the trabecular bone region and was not expressed in the perichondrium or periosteum. Mesenchymal cells retaining high CTGF reporter expression were adjacent to, but distinct from mature osteoblasts lining bone surfaces and endothelial cells forming the vascular sinuses. Comparison of CTGF and Osterix reporter expression in bone tissue sections indicated an inverse correlation between the strength of CTGF expression and osteoblast maturation. Down-regulation of CTGF reporter expression also occurred during in vitro osteogenic differentiation. Collectively, our studies indicate that CTGF reporter mice selectively identify a subpopulation of bone marrow mesenchymal progenitor cells that reside in the trabecular bone region.
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Strecker
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, USA.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, USA.
authors.forename: Fayekah
authors.initials: F
authors.lastname: Assanah
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, USA.
authors.forename: Spenser
authors.initials: S
authors.lastname: Smith
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, USA. Electronic address: pmaye@neuron.uchc.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Maye
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D039902:Multipotent Stem Cells / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: C526318:CCN2 protein, mouse; C485184:enhanced green fluorescent protein; D055513:Connective Tissue Growth Factor; D049452:Green Fluorescent Proteins
keywords: Bone marrow; Connective tissue; Mesenchymal stem cell; Stromal cell