Systemic Lupus Erythematosus Model Mouse Bone Marrow Mesenchymal Stem Cells Participate In The Study Of Hematopoietic Injury

Objective To investigate the hematological changes in MRL/lpr lupus mice and detect the expression of adhesion molecule N-cadherin in their bone marrow mesenchymal stem cells(BMMSCs),and the regulation of BMMSCs on hematopoiesis.Methods Peripheral blood count of lupus mice was analyzed.Blood cells percentage of each lineage in bone marrow was analyzed by flow cytometry.Bone marrow CFU-pre-B,BFU-E and CFU-GM colony formation assay were performed.N-cadherin expression in BMMSCs was analyzed by Western blot before and after treating BMMSCs with the BMP/Smads pathway agonist BMP-2 and inhibitor Noggin.BMMSCs from MRL/lpr lupus mice and C57BL/6 mice were used as feeder cells,and normal mouse Sca-1+ bone marrow hematopoietic stem cells were sorted by magnetic beads.After 14 days of co-culture,analyze the fomatoin of CFU-pre-B,CFU-GM,BFU-E and the percentage of myeloid lineage(CD11b+),B-lymphocytes(B220+),T-lymphocytes(CD3e+)and erythroid lineage(Terl 19+).Results Hemoglobin,red blood cell count and hematocrit were decreased in lupus mice compared with C57BL/6 mice(P <0.01).The percentage of B220+ lymphocytes and the number of CFU-pre-B in bone marrow of lupus mice was decreased compared with the control group(P <0.05).Expression of N-cadherin in BMMSC of lupus mice was higher compared with the control group(P<0.05).Expression of N-cadherin was decreased in BMP-2treated BMMSC and increased after Noggin treatment(P<0.05).After co-cultured with BMMSCs for 2 weeks,Sca-1+ bone marrow hematopoietic stem cells supported by BMMSCs of lupus mice formed higher number of CFU-pre-B,CFU-GM and total colonies(P <0.01).The proportion of B220+ cells was higher compared with the control group,and the proportion of CD11b+ cells was decreased(P<0.01).Conclusion Hematological changes in lupus mice include anemia and impaired bone marrow B lymphocytes production.The expression of N-cadherin in BMMSCs of lupus mice is increased and can be regulated by BMP signaling pathway.Inhibition of the BMP signaling pathway can result in increased N-cadherin expression.BMMSCs of lupus mice can promote the proliferation of normal bone marrow Sca-1+ hematopoietic stem cells and their differentiation into B lymphoid progenitors and granulocyte-macrophage progenitors...