Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells

Shunya Kondo, Chisa Shukunami, Yoko Morioka, Naoya Matsumoto, Rei Takahashi, Junseo Oh, Tadao Atsumi, Akihiro Umezawa, Akira Kudo, Hitoshi Kitayama, Yuji Hiraki, Makoto Noda

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36 Citations (Scopus)

Abstract

Extracellular matrix (ECM) undergoes continuous remodeling during mammalian development. Although involvement of matrix metalloproteinases (MMPs) in ECM degradation has been well documented, how this process is regulated to allow proper ECM accumulation remains unclear. We previously showed the involvement of a membrane-anchored MMP regulator, RECK (reversion-inducing cysteine-rich protein with Kazal motifs), in vascular development in mice. Here we report that Reck mRNA can be detected in developing cartilage in E13.5-16.5 mouse embryos and is progressively upregulated during differentiation of a chondrogenic cell line ATDC5 in vitro. In the early phase of ATDC5 differentiation, RECK expression stays low, multiple MMPs are upregulated, and there is ECM degradation at the sites of cellular condensation. In the later phase, RECK is upregulated inside the expanding cartilaginous nodules where type II collagen is accumulated while active ECM degradation persists along the rim of the nodules. Constitutive RECK expression suppressed initial cellular condensation, whereas RECK knockdown suppressed the later ECM accumulation in the cartilaginous nodules. These results suggest that RECK expression at the right place (in the core of the nodules) and at the right time (only in the later phase) is important for proper chondrogenesis and that RECIC, together with MMPs, plays a crucial role in regulating dynamic processes of tissue morphogenesis.

Original languageEnglish
Pages (from-to)849-857
Number of pages9
JournalJournal of Cell Science
Volume120
Issue number5
DOIs
Publication statusPublished - 2007 Mar 1

Keywords

  • Chondrogenesis
  • ECM remodeling
  • MMP
  • RECK
  • Tissue morphogenesis

ASJC Scopus subject areas

  • Cell Biology

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    Kondo, S., Shukunami, C., Morioka, Y., Matsumoto, N., Takahashi, R., Oh, J., Atsumi, T., Umezawa, A., Kudo, A., Kitayama, H., Hiraki, Y., & Noda, M. (2007). Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells. Journal of Cell Science, 120(5), 849-857. https://doi.org/10.1242/jcs.03388