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7164998 
Journal Article 
Homocysteine attenuates the expression of osteocalcin but enhances osteopontin in MC3T3-E1 preosteoblastic cells 
Sakamoto, W; Isomura, H; Fujie, K; Deyama, Y; Kato, A; Nishihira, J; Izumi, H; , 
2005 
1 
Biochimica et Biophysica Acta
ISSN: 0006-3002
EISSN: 1878-2434 
ELSEVIER SCIENCE BV 
AMSTERDAM 
12-16 
English 
15878736 
WOS:000229350700002 
It has been pointed out that very high plasma levels of homocysteine are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. However, it is unclear by which mechanism hyperhomocysteine induces osteoporosis, although it is known to interfere with the formation of cross-links in collagen, an essential process in bone formation. Therefore, we investigated the effect of homcysteine on expression of osteocalcin and osteopontin in MC3T3-E1 preosteoblastic cells. Confluent cells were grown in RPMI 1640 containing 10% fetal calf serum with or without homocysteine in an atmosphere of 95% humidified air, 5% CO2 at 37 degrees C. The secretion of osteocalcin from the cells increased time-dependently until the end of culture (day 34), but 500 microM homocysteine led to an approximately 61% decrease for osteocalcin after 19 days of culture as compared with the control. On the other hand, osteopontin was not inhibited by 500 microM homocysteine but rather activated, and ranged from 134%-209% of the control level in the period from 10 days until the end of culture. From analysis of RT-PCR for mRNA of osteocalcin and osteopontin at the end of the culture, homocysteine levels of 100 and 500 microM significantly increased the expression of osteopontin mRNA with the control (p < 0.05). In contrast, the expression of osteopontin mRNA was suppressed in a dose-dependent manner, showing a mirror image of the effect on osteopontin mRNA. These findings suggest that hyperhomocystenemia appears to be an independent risk factor for osteoporosis by disturbing osteoblast function.