Interaction between cartilage oligomeric matrix protein and extracellular matrix protein 1 mediates endochondral bone growth.
In an effort to define the biological functions of COMP, a functional genetic screen was performed. This led to the identification of extracellular matrix protein 1 (ECM1) as a novel COMP-associated partner. COMP directly binds to ECM1 both in vitro and in vivo. The EGF domain of COMP and the C-terminus of ECM1 mediate the interaction between them. COMP and ECM1 colocalize in the growth plates invivo. ECM1 inhibits chondrocyte hypertrophy, matrix mineralization, and endochondral bone formation, and COMP overcomes the inhibition by ECM1. In addition, COMP-mediated neutralization of ECM1 inhibition depends on their interaction, since COMP largely fails to overcome the ECM1 inhibition in the presence of the EGF domain of COMP, which disturbs the association of COMP and ECM1. These findings provide the first evidence linking the association of COMP and ECM1 and the biological significance underlying the interaction between them in regulating endochondral bone growth.
Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY 10003, United States.
Li
L
Kong
Qingyun
Q
Tian
Fengjin
F
Guo
Maria T
MT
Mucignat
Roberto
R
Perris
Sandy
S
Sercu
Joseph
J
Merregaert
Paul E
PE
Di Cesare
Chuan-Ju
CJ
Liu
D000818:Animals; D001846:Bone Development / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism*; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins; D005333:Fetus / Q000196:embryology; D006023:Glycoproteins; D006128:Growth / Q000235:genetics; D006132:Growth Plate / Q000378:metabolism; D064235:Matrilin Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000235:genetics; D011485:Protein Binding / Q000235:genetics
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins