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First published online 13 February 2007
doi: 10.1242/jcs.03388

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

Shunya Kondo^1,2, Chisa Shukunami², Yoko Morioka¹, Naoya Matsumoto^1,3, Rei Takahashi⁴, Junseo Oh^1,*, Tadao Atsumi⁵, Akihiro Umezawa⁶, Akira Kudo⁷, Hitoshi Kitayama¹, Yuji Hiraki² and Makoto Noda^1,

¹ Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
² Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
³ Department of Anatomy and Neurobiology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
⁴ Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
⁵ Antibiotics Laboratory, Discovery Research Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan
⁶ Department of Reproductive Biology and Pathology, National Research Institute for Child and Health Development, Okura, Setagaya, 157-8535 Tokyo, Japan
⁷ Department of Biological Information, Tokyo Institute of Technology, Nagatsuda, Midori-ku, Yokohama, 226-8501, Japan

Author for correspondence (e-mail: mnoda{at}virus.kyoto-u.ac.jp)

Accepted 3 January 2007

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 E13.516.5 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 RECK, together with MMPs, plays a crucial role in regulating dynamic processes of tissue morphogenesis.

Key words: RECK, MMP, ECM remodeling, Tissue morphogenesis, Chondrogenesis