Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Hwanhee Oh, Je Hwang Ryu, Jimin Jeon, Siyoung Yang, Churl Hong Chun, Hongryeol Park, Hyung Joon Kim, Woo Shin Kim, Hong Hee Kim, Young-Guen Kwon, Jang Soo Chun

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Developing cartilage serves as a template for long-bone development during endochondral ossification. Although the coupling of cartilage and bone development with angiogenesis is an important regulatory step for endochondral ossification, the molecular mechanisms are poorly understood. One possible mechanism involves the action of Dickkopf (DKK), which is a family of soluble canonical Wnt antagonists with four members (DKK1-4). We initially observed opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite specific expression pattern during cartilage development, chondrocyte- and hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal developmental phenotypes. However, Dkk1 misexpression in endothelial cells resulted in defects of endochondral ossification and reduced skeletal size. The defects are caused by the inhibition of angiogenesis in developing bone and subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage resorption.

Original languageEnglish
Pages (from-to)1335-1344
Number of pages10
JournalJournal of Bone and Mineral Research
Volume27
Issue number6
DOIs
Publication statusPublished - 2012 Jan 1

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Chondrocytes
Osteogenesis
Endothelial Cells
Cartilage
Bone Development
Transgenic Mice
Up-Regulation
Down-Regulation
Apoptosis
Phenotype
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Oh, Hwanhee ; Ryu, Je Hwang ; Jeon, Jimin ; Yang, Siyoung ; Chun, Churl Hong ; Park, Hongryeol ; Kim, Hyung Joon ; Kim, Woo Shin ; Kim, Hong Hee ; Kwon, Young-Guen ; Chun, Jang Soo. / Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification. In: Journal of Bone and Mineral Research. 2012 ; Vol. 27, No. 6. pp. 1335-1344.
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Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification. / Oh, Hwanhee; Ryu, Je Hwang; Jeon, Jimin; Yang, Siyoung; Chun, Churl Hong; Park, Hongryeol; Kim, Hyung Joon; Kim, Woo Shin; Kim, Hong Hee; Kwon, Young-Guen; Chun, Jang Soo.

In: Journal of Bone and Mineral Research, Vol. 27, No. 6, 01.01.2012, p. 1335-1344.

Research output: Contribution to journalArticle

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AU - Oh, Hwanhee

AU - Ryu, Je Hwang

AU - Jeon, Jimin

AU - Yang, Siyoung

AU - Chun, Churl Hong

AU - Park, Hongryeol

AU - Kim, Hyung Joon

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AU - Kim, Hong Hee

AU - Kwon, Young-Guen

AU - Chun, Jang Soo

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