Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3–green fluorescent protein reporter mice

Yu Mori, Douglas Adams, Yusuke Hagiwara, Ryu Yoshida, Masayuki Kamimura, Eiji Itoi, David W. Rowe

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)606-614
Number of pages9
JournalJournal of Bone and Mineral Metabolism
Volume34
Issue number6
DOIs
Publication statusPublished - 2016 Nov 1

Keywords

  • Chondrocytes
  • Dickkopf-related protein 3
  • Fibrocartilage
  • Fracture healing
  • Osteoblasts

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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