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

National Research Institute for Child Health and Development, Tokyo, Edo, Tōkyō, Japan
Journal of Cell Science (Impact Factor: 5.43). 04/2007; 120(Pt 5):849-57. DOI: 10.1242/jcs.03388
Source: PubMed


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 approximately 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.

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Available from: Naoya Matsumoto, Dec 24, 2015
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    • "In contrast to normal epithelium, EMT reflects the loss of cellular adherence and contact growth, involving dysregulation of adhesion molecules and increased breakdown of the extracellular matrix by matrix metalloproteinases (MMPs) (Guarino et al., 2007; Neth et al., 2007). MMPs are a family of zinc-dependent proteinases that degrade most extracellular matrix components (Kondo et al., 2007). Approximately 20 members of the MMP family have been identified, sharing common structural and functional elements (Zucker and Vacirca, 2004). "
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    • "The RECK gene encodes a membrane-anchored glycoprotein capable of regulating several members of the MMP family (MMP2, MMP7, MMP9, and MT1-MMP)6789 and some other extracellular metalloproteinases such as CD13/aminopeptidase N and ADAM10810. RECK is expressed in multiple normal tissues, including developing vasculature, skeletal muscles, neuromuscular junctions, cartilage, fibroblasts, and neural precursor cells710111213. In cultured mouse embryo fibroblasts, RECK was found to be required for proper cell-substrate adhesion and persistent directional migration14. "
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    • "Finally, the underlying mesenchymal cells and the ECM appear to have decreased integrity compared to those underlying the DE of the control limb buds (Fig. 2D panels 12 and 11; supplementary material Fig. S2). Our previous study implicated Reck in chondrocyte differentiation in vitro (Kondo et al., 2007). To test whether reduced Reck expression in developing cartilage is responsible for the skeletal phenotype of low-Reck mice, we generated mutant mice (R1/-;Col2a1-Cre) in which Reck is inactivated selectively in the late-stage mesenchymal cells committed to the chondrocyte lineage. "
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