Bone morphogenetic protein signaling in articular chondrocyte differentiation

Ayako Nishihara, Makiko Fujii, T. Kuber Sampath, Kohei Miyazono, A Hari Reddi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Articular chondrocytes progressively undergo dedifferentiation into a spindle-shaped mesenchymal cellular phenotype in monolayers. Chondrocyte dedifferentiation is stimulated by retinoic acid. On the other hand, bone morphogenic proteins (BMPs) stimulate differentiation of chondrocytes. We examined the mechanism of effects of BMP in chondrocyte differentiation with use of a recombinant adenovirus vector system. Constitutively active forms of BMP type I receptors (BMPR-IA and BMPR-IB) and those of activin receptor-like kinase (ALK)-1 and ALK-2 maintained differentiation of chondrocytes in the presence of retinoic acid. The BMP receptor-regulated signaling substrates, Smad1/5, weakly induced chondrocyte differentiation; the effects of Smad1/5 were enhanced by BMP-7 treatment. Inhibitory Smad, Smad6, blocked increase of expression of chondrocyte markers by BMP-7 in a dose-dependent manner. SB202190, a p38 mitogen-activated protein kinase inhibitor, inhibited this effect of BMP-7; however, since SB202190 suppressed phosphorylation of Smad1/5, this may be due to blockade of BMP receptor activation. These results together strongly suggest that induction of chondrocyte differentiation by BMP-7 is regulated by Smad pathways.

Original languageEnglish (US)
Pages (from-to)617-622
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume301
Issue number2
DOIs
StatePublished - Feb 7 2003

Fingerprint

Bone Morphogenetic Proteins
Chondrocytes
Bone
Joints
Bone and Bones
Proteins
Type I Bone Morphogenetic Protein Receptors
Activin Receptors
Tretinoin
Hand Bones
Phosphorylation
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Adenoviridae
Monolayers
Chemical activation
Phenotype

Keywords

  • BMP-7
  • Chondrocytic differentiation
  • Retinoic acid
  • Smad

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Bone morphogenetic protein signaling in articular chondrocyte differentiation. / Nishihara, Ayako; Fujii, Makiko; Sampath, T. Kuber; Miyazono, Kohei; Reddi, A Hari.

In: Biochemical and Biophysical Research Communications, Vol. 301, No. 2, 07.02.2003, p. 617-622.

Research output: Contribution to journalArticle

Nishihara, Ayako ; Fujii, Makiko ; Sampath, T. Kuber ; Miyazono, Kohei ; Reddi, A Hari. / Bone morphogenetic protein signaling in articular chondrocyte differentiation. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 301, No. 2. pp. 617-622.
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