Protein-S, a vitamin K-dependent protein, is a bone matrix component synthesized and secreted by osteoblasts.
Protein-S is a vitamin K (Vit K)-dependent protein synthesized by hepatocytes, megakaryocytes, and endothelial cells and plays an important role in the regulation of hemostasis. Two cases of free protein-S congenital deficiency were recently reported to be associated with osteopenia. We hypothesized that this osteopenia could be the result of a bone deficit of protein-S synthesized by bone cells. Using enzyme-linked immunoassay, immunocytochemistry, immunoblotting, and immunoprecipitation after labeling with [35S]methionine, we have shown that this protein is secreted by three human osteosarcoma cell lines and by human adult osteoblast-like cells. In addition, protein-S was present in protein extracts of human bone matrix. Protein-S secreted by MG 63 cells increased linearly from 1-7 days of culture, was biologically active, and was regulated by warfarin, as previously described for the other cell types secreting protein-S. Vit K had no direct effect on protein-S secretion or activity, but could overcome the effects of warfarin. In conclusion, in addition to osteocalcin and matrix gamma-carboxyglutamic acid (Gla) protein, osteoblasts secrete another Vit K-dependent protein, which is a constituent of the bone matrix. Our data suggest that osteopenia occurring in patients with congenital protein-S deficiency might be related to a deficiency of protein-S secretion by the osteoblasts. This finding raises the intriguing possibility that protein-S might play a role in bone turnover and bone mass.
Maillard
C
C
Inserm U 234, Hôpital Edouard Herriot, Lyon, France.
Berruyer
M
M
Serre
C M
CM
Dechavanne
M
M
Delmas
P D
PD
D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008715:Methionine / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015675:Osteocalcin / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D011233:Precipitin Tests; D017293:Protein S; D013462:Sulfur Radioisotopes; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D006023:Glycoproteins; D017293:Protein S; D013462:Sulfur Radioisotopes; D015675:Osteocalcin; D008715:Methionine