Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB.
Signaling pathways involved in oxidative stress-induced inhibition of osteoblast differentiation are not known. We showed in this report that H(2)O(2) (0.1-0.2mM)-induced oxidative stress suppressed the osteoblastic differentiation process of primary rabbit bone marrow stromal cells (BMSC) and calvarial osteoblasts, manifested by a reduction of differentiation markers including alkaline phosphatase (ALP), type I collagen, colony-forming unit-osteoprogenitor (CFU-O) formation, and nuclear phosphorylation of Runx2. H(2)O(2) treatment stimulated phospholipase C-gamma1 (PLC-gamma1), extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-kappaB signaling but inhibited p38 mitogen-activated protein kinase (MAPK) activation. In the presence of 20microM PD98059 or 50microM caffeic acid phenethyl ester (CAPE), specific inhibitor for ERKs or NF-kappaB, respectively, could significantly reverse the decrease of above-mentioned osteoblastic differentiation markers elicited by H(2)O(2) (0.1mM). Furthermore, PD98059 also suppressed H(2)O(2)-stimulated NF-kappaB signaling in this process. These data suggest that ERK and ERK-dependent NF-kappaB activation is required for oxidative stress-induced inhibition of osteoblastic differentiation in rabbit BMSC and calvarial osteoblasts.
Bai
Xiao-chun
XC
Department of Cell Biology, The First Military Medical University, Guangzhou, PR China.
Lu
Di
D
Bai
Jie
J
Zheng
Hang
H
Ke
Zi-yong
ZY
Li
Xiao-ming
XM
Luo
Shen-qiu
SQ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*
D016328:NF-kappa B; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases