title: Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3-green fluorescent protein reporter mice.
abstract: Fracture healing is a complex biological process involving the proliferation of mesenchymal progenitor cells, and chondrogenic, osteogenic, and angiogenic differentiation. The mechanisms underlying the proliferation and differentiation of mesenchymal progenitor cells remain unclear. Here, we demonstrate Dickkopf-related protein 3 (Dkk3) expression in periosteal cells using Dkk3-green fluorescent protein reporter mice. We found that proliferation of mesenchymal progenitor cells began in the periosteum, involving Dkk3-positive cell proliferation near the fracture site. In addition, Dkk3 was expressed in fibrocartilage cells together with smooth muscle α-actin and Col3.6 in the early phase of fracture healing as a cell marker of fibrocartilage cells. Dkk3 was not expressed in mature chondrogenic cells or osteogenic cells. Transient expression of Dkk3 disappeared in the late phase of fracture healing, except in the superficial periosteal area of fracture callus. The Dkk3 expression pattern differed in newly formed type IV collagen positive blood vessels and the related avascular tissue. This is the first report that shows Dkk3 expression in the periosteum at a resting state and in fibrocartilage cells during the fracture healing process, which was associated with smooth muscle α-actin and Col3.6 expression in mesenchymal progenitor cells. These fluorescent mesenchymal lineage cells may be useful for future studies to better understand fracture healing.
authors.affiliation: Center for Regenerative Medicine and Skeletal Biology, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA. yu-mori@med.tohoku.ac.jp.|Department of Orthopaedic Surgery, Graduate School of Tohoku University, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan. yu-mori@med.tohoku.ac.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Center for Regenerative Medicine and Skeletal Biology, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Adams
authors.affiliation: Center for Regenerative Medicine and Skeletal Biology, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hagiwara
authors.affiliation: Center for Regenerative Medicine and Skeletal Biology, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Ryu
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Tohoku University, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kamimura
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Tohoku University, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
authors.affiliation: Center for Regenerative Medicine and Skeletal Biology, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Rowe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002146:Bony Callus / Q000378:metabolism* / Q000473:pathology; D058948:Cell Tracking; D051445:Fibrocartilage / Q000378:metabolism* / Q000473:pathology; D017102:Fracture Healing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010521:Periosteum / Q000378:metabolism* / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C405061:Dkk3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D049452:Green Fluorescent Proteins
keywords: Chondrocytes; Dickkopf-related protein 3; Fibrocartilage; Fracture healing; Osteoblasts