title: Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells.
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 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.
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Kondo
authors.forename: Chisa
authors.initials: C
authors.lastname: Shukunami
authors.forename: Yoko
authors.initials: Y
authors.lastname: Morioka
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Rei
authors.initials: R
authors.lastname: Takahashi
authors.forename: Junseo
authors.initials: J
authors.lastname: Oh
authors.forename: Tadao
authors.initials: T
authors.lastname: Atsumi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kitayama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiraki
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D020868:Gene Silencing; D015151:Immunoblotting; D017403:In Situ Hybridization; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009154:Mutation / Q000235:genetics / Q000502:physiology
chemical_list: D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C492025:Reck protein, mouse; D003094:Collagen; D020782:Matrix Metalloproteinases