N-acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells.
Estrogen deficiency causes osteoporosis via increased generation of reactive oxygen species (ROS), and thus, antioxidants may prove to be the effective therapeutic candidates. We examined the effects of the antioxidant N-acetylcysteine (NAC) on osteoblastic differentiation in mouse calvarial cells. NAC (10-30 mM) enhanced alkaline phosphatase activity, mRNA expression of osteoblast differentiation-associated genes and mineralized nodule formation. It also increased expression of bone morphogenetic proteins-2, -4, and -7. The osteogenic activity of NAC was partially reduced by inhibition of glutathione synthesis. Since caffeic acid phenethyl ester did not stimulate osteoblast differentiation, it is unlikely that ROS scavenging activity of NAC is sufficient for osteogenic activity. We observed that NAC suppressed small GTPase RhoA activity and activation of RhoA by Pasteurella multocida toxin suppressed the osteogenic activity of NAC. These results suggest that NAC might exert its osteogenic activity via increased glutathione synthesis and inhibition of RhoA activation.
Jun
Ji Hae
JH
Department of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Republic of Korea.
Lee
Sun-Hwan
SH
Kwak
Han Bok
HB
Lee
Zang Hee
ZH
Seo
Sang-Beum
SB
Woo
Kyung Mi
KM
Ryoo
Hyun-Mo
HM
Kim
Gwan-Shik
GS
Baek
Jeong-Hwa
JH
D000111:Acetylcysteine / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D012886:Skull / Q000166:cytology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
D000975:Antioxidants; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D019485:Bone Morphogenetic Proteins; D002109:Caffeic Acids; C062258:Pasteurella multocida toxin; D000469:Alkaline Phosphatase; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C055494:caffeic acid phenethyl ester; D005978:Glutathione; D010626:Phenylethyl Alcohol; D000111:Acetylcysteine