Expression of TNF-α/NF-κB signaling pathway in the bone of systemic lupus erythematosus mice (MRL/lpr)
CUI Ting1, SONG Dong-ming1, QIU Ying-ying1, RUI Jin-bing1, WU Ling1, FEI Xiao-ming2, LI Jing1, TANG Yu1
(1. Department of Rheumatology and Immunology, 2. Department of Hematology, the Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China)
Abstract：Objective: To investigate the tumor necrosis factor-α(TNF-α)/nuclear factor-κB p50 (NF-κB p50)signaling pathway in bone of systemic lupus erythematosus mice (MRL/lpr). Methods: Six C3He/HeJ mice (control group) and six MRL/lpr mice (lupus group) were feed, then mouse femur tissue sections were prepared and bone circumstances were observed by hematoxylin-eosin (HE) staining. The proteins of TNF-α and NF-κB p50 were detected by immunohistochemical staining. Bone marrow mesenchymal stem cells (BMMSCs) were isolated by density gradient centrifugation adherence screening method and cultured, then the expressions of TNF-α, NF-κB p50 were detected by immunocytochemistry staining. Results: Trabecular bone of MRL/lpr lupus mice showed osteoporosis and the percentage of the cortex to the volume of bone of MRL/lpr mice were significantly lower compared to control group (P<0.05). The protein expression levels of TNF-α and NF-κB p50 on the femur of MRL/lpr mice were higher than the C3He/HeJ mice (P<0.05 or P<0.01). Immunocytochemistry results displayed that on the BMMSCs of the MRL/lpr mice, the protein expression levels of TNF-α and NF-κB p50 were also higher than the C3He/HeJ mice (P<0.05 or P<0.01). Conclusion: TNF-α/NF-κB signaling pathway on the bone of lupus mice has been abnormally activated.
\[1\]García-Carrasco M, Mendoza-Pinto C, Escárcega RO, et al. Osteoporosis in patients with systemic lupus erythematosus\[J\]. Isr Med Assoc J, 2009, 11(8): 486-491.［2］Tang Y, Xie H, Chen J, et al. Activated NFκB in bone marrow mesenchymal stem cells from systemic lupus erythematosus patients inhibits osteogenic differentiation through downregulating Smad signaling\[J\]. Stem Cells Dev, 2013, 22(4): 668-678.［3］Tanaka Y. Secondary osteoporosis or secondary contributors to bone loss in fracture. The relevance of immune system to bone metabolism\[J\]. Clin Calcium, 2013, 23(9): 1265-1270.［4］He X, Dziak R, Yuan X, et al. BMP2 genetically engineered MSCs and EPCs promote vascularized bone regeneration in rat critical-sized calvarial bone defects\[J\]. PLoS ONE, 2013, 8(4): e60473.［5］Sun L, Akiyama K, Zhang H, et al. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans\[J\].Stem Cells, 2009, 27(6): 1421-1432.［6］Hess K, Ushmorov A, Fiedler J, et al. TNFα promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-κB signaling pathway\[J\]. Bone,2009, 45(2): 367-376.［7］Tsukahara S, Ikeda R, Goto S, et al. Tumour necrosis factor α-stimulated gene-6 inhibits osteoblastic differentiation of human mesenchymal stem cells induced by osteogenic differentiation medium and BMP-2\[J\]. Biochem J, 2006, 398(3): 595-603.［8］Mukai T, Otsuka F, Otani H, et al. TNF-α inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling\[J\]. Biochem Biophys Res Commun, 2007, 356(4): 1004-1010.［9］David JP, Schett G. TNF and bone\[J\]. Curr Dir Autoimmun, 2010, 11: 135-144.
2014, Vol. 24 
