Abstract:
:Osteoblasts regulate bone formation and remodeling, and are main target cells of oxidative stress in the progression of osteonecrosis. The stem cell factor (SCF)-c-Kit pathway plays important roles in the proliferation, differentiation and survival in a range of cell types, but little is known about its functions in osteoblasts. In this study, we found that c-Kit is functionally expressed in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Its ligand SCF exerted significant cyto-protective effects against hydrogen peroxide (H₂O₂). SCF activated its receptor c-Kit in osteoblasts, which was required for its cyto-protective effects against H₂O₂. Pharmacological inhibition (by Imatinib and Dasatinib) or shRNA-mediated knockdown of c-Kit thus inhibited SCF-mediated osteoblast protection. Further investigations showed that protection by SCF against H₂O₂ was mediated via activation of c-Kit-dependent Akt pathway. Inhibition of Akt activation, through pharmacological or genetic means, suppressed SCF-mediated anti-H₂O₂ activity in osteoblasts. In summary, we have identified a new SCF-c-Kit-Akt physiologic pathway that protects osteoblasts from H₂O₂-induced damages, and might minimize the risk of osteonecrosis caused by oxidative stress.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Yang L,Wu Z,Yin G,Liu H,Guan X,Zhao X,Wang J,Zhu Jdoi
10.1016/j.bbrc.2014.11.002subject
Has Abstractpub_date
2014-12-12 00:00:00pages
256-61issue
3-4eissn
0006-291Xissn
1090-2104pii
S0006-291X(14)01984-6journal_volume
455pub_type
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