Metallothionein protects bone marrow stromal cells against hydrogen peroxide-induced inhibition of osteoblastic differentiation.
Metallothionein (MT), a cysteine-rich, metal-binding protein, is involved in homeostatic regulation of essential metals and protection of cells against oxidative injury. It has been shown that oxidative stress is associated with pathogenesis of osteoporosis and is capable of inhibiting osteoblastic differentiation of bone cells by nuclear factor-kappaB (NF-kappaB). In this study, the effect of MT on oxidative stress-induced inhibition of osteoblast differentiation was examined. 50-200 microM hydrogen peroxide-induced oxidative stress suppressed the osteoblastic differentiation process of primary mouse bone marrow stromal cells (BMSCs), manifested by a reduction in the differentiation marker alkaline phosphatase (ALP). The presence of exogenous MT (20-500 microM) or induction of endogenous MT by ZnCl2 (50-200 microM) could protect BMSCs against H2O2-induced inhibition of osteoblastic differentiation, manifested by a resumption of H2O2-inhibited ALP activity and ALP positive cells. Furthermore, adding exogenous MT or inducing endogenous MT expression impaired H2O2-stimulated NF-kappaB signaling. These data indicate the ability of MT to protect BMSCs against oxidative stress-induced inhibition of osteoblastic differentiation.
Liu
An-Ling
AL
Yingdong College of Biotechnology, Shaoguan University, Shaoguan, Guangdong Province 512005, PR China. anlingliu@yahoo.com.cn
Zhang
Zhong-Ming
ZM
Zhu
Bi-Feng
BF
Liao
Zhao-Hui
ZH
Liu
Zhu
Z
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D010024:Osteoporosis / Q000378:metabolism / Q000503:physiopathology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology
D015415:Biomarkers; D002712:Chlorides; D016328:NF-kappa B; D016877:Oxidants; D017967:Zinc Compounds; C016837:zinc chloride; D008668:Metallothionein; D006861:Hydrogen Peroxide; D000469:Alkaline Phosphatase