Nephronectin promotes osteoblast differentiation via the epidermal growth factor-like repeats.
We found that nephronectin was significantly down-regulated by TGF-beta1. To determine the function of nephronectin in osteogenesis, we generated various constructs to produce stable MC3T3-E1 cell lines, expressing and secreting nephronectin protein, including full-length (Npnt), lacking EGF-like repeats (Np-MAM), and lacking RGD and MAM domains (Np-EGF). We demonstrated that nephronectin promotes differentiation during osteoblast differentiation and the EGF-like repeats were essential. Lack of these repeats resulted in inhibiting the change in morphology. Over-expression of nephronectin results in earlier formation of bone nodules than the vector control. ERK activation is essential for nephronectin-induced osteoblast differentiation.
Kahai
Shireen
S
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Lee
Shao-Chen
SC
Seth
Arun
A
Yang
Burton B
BB
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000235:genetics / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis; D010766:Phosphorylation; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics / Q000502:physiology*
D016326:Extracellular Matrix Proteins; C432915:nephronectin; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases