RRC ID 36760
Author Li C, Shi C, Kim J, Chen Y, Ni S, Jiang L, Zheng C, Li D, Hou J, Taichman RS, Sun H.
Title Erythropoietin promotes bone formation through EphrinB2/EphB4 signaling.
Journal J Dent Res
Abstract Recent studies have demonstrated that erythropoietin (EPO) has extensive nonhematopoietic biological functions. However, little is known about how EPO regulates bone formation, although several studies suggested that EPO can affect bone homeostasis. In this study, we investigated the effects of EPO on the communication between osteoclasts and osteoblasts through the ephrinB2/EphB4 signaling pathway. We found that EPO slightly promotes osteoblastic differentiation with the increased expression of EphB4 in ST2 cells. However, EPO increased the expression of Nfatc1 and ephrinB2 but decreased the expression of Mmp9 in RAW264.7 cells, resulting in an increase of ephrinB2-expressing osteoclasts and a decrease in resorption activity. The stimulation of ephrinB2/EphB4 signaling via ephrinB2-Fc significantly promoted EPO-mediated osteoblastic differentiation in ST2 cells. EphB4 knockdown through EphB4 shRNA inhibited EPO-mediated osteoblastic phenotypes. Furthermore, in vivo assays clearly demonstrated that EPO efficiently induces new bone formation in the alveolar bone regeneration model. Taken together, these results suggest that ephrinB2/EphB4 signaling may play an important role in EPO-mediated bone formation.
Volume 94(3)
Pages 455-63
Published 2015-3-1
DOI 10.1177/0022034514566431
PII 0022034514566431
PMID 25586589
PMC PMC4336159
MeSH Alveolar Process / drug effects Animals Bone Regeneration / drug effects Cell Culture Techniques Cell Differentiation / drug effects Cell Line Ephrin-B2 / drug effects* Erythropoietin / pharmacology* Erythropoietin / therapeutic use Gene Knockdown Techniques Gene Silencing Incisor / surgery Macrophages / drug effects Male Matrix Metalloproteinase 9 / drug effects Mesenchymal Stem Cells / drug effects Mice NFATC Transcription Factors / drug effects Osteoblasts / drug effects Osteoclasts / drug effects Osteogenesis / drug effects* RNA, Small Interfering / administration & dosage Random Allocation Rats Rats, Wistar Receptor, EphB4 / drug effects* Signal Transduction / drug effects Tooth Extraction Tooth Socket / drug effects
IF 4.914
Times Cited 38
WOS Category DENTISTRY, ORAL SURGERY & MEDICINE
Resource
Human and Animal Cells ST2(RCB0224)