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

被引:41
作者
Kondo, Shunya
Shukunami, Chisa
Morioka, Yoko
Matsumoto, Naoya
Takahashi, Rei
Oh, Junseo
Atsumi, Tadao
Umezawa, Akihiro
Kudo, Akira
Kitayama, Hitoshi
Hiraki, Yuji
Noda, Makoto [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Mol Oncol, Sakyo Ku, Kyoto 6068501, Japan
[2] Kyoto Univ, Inst Frontier Med Sci, Dept Cellular Differentiat, Sakyo Ku, Kyoto 6068507, Japan
[3] Kyoto Univ, Grad Sch Med, Dept Anat & Neurobiol, Kyoto 6068501, Japan
[4] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Sakyo Ku, Kyoto 6068501, Japan
[5] RIKEN, Discovery Res Inst, Antibiot Lab, Wako, Saitama 3510198, Japan
[6] Natl Res Inst Child Hlth & Dev, Dept Reprod Biol & Pathol, Tokyo 1578535, Japan
[7] Tokyo Inst Technol, Dept Biol Informat, Yokohama, Kanagawa 2268501, Japan
关键词
RECK; MMP; ECM remodeling; tissue morphogenesis; chondrogenesis;
D O I
10.1242/jcs.03388
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 similar to 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 RECK, together with MMPs, plays a crucial role in regulating dynamic processes of tissue morphogenesis.
引用
收藏
页码:849 / 857
页数:9
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