The cleavage of N-cadherin is essential for chondrocyte differentiation.
The aggregation of chondroprogenitor mesenchymal cells into precartilage condensation represents one of the earliest events in chondrogenesis. N-cadherin is a key cell adhesion molecule implicated in chondrogenic differentiation. Recently, ADAM10-mediated cleavage of N-cadherin has been reported to play an important role in cell adhesion, migration, development and signaling. However, the significance of N-cadherin cleavage in chondrocyte differentiation has not been determined. In the present study, we found that the protein turnover of N-cadherin is accelerated during the early phase of chondrogenic differentiation in ATDC5 cells. Therefore, we generated the subclones of ATDC5 cells overexpressing wild-type N-cadherin, and two types of subclones overexpressing a cleavage-defective N-cadherin mutant, and examined the response of these cells to insulin stimulation. The ATDC5 cells overexpressing cleavage-defective mutants severely prevented the formation of cartilage aggregates, proteoglycan production and the induction of chondrocyte marker gene expression, such as type II collagen, aggrecan and type X collagen. These results suggested that the cleavage of N-cadherin is essential for chondrocyte differentiation.
Nakazora
Shigeto
S
Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu-city, Mie 514-8507, Japan.
Matsumine
Akihiko
A
Iino
Takahiro
T
Hasegawa
Masahiro
M
Kinoshita
Ayae
A
Uemura
Kengo
K
Niimi
Rui
R
Uchida
Atsumasa
A
Sudo
Akihiro
A
D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011509:Proteoglycans / Q000378:metabolism
D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D008565:Membrane Proteins; D011509:Proteoglycans; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human