The Rescue Effect of RANKL on Zoledronate Induced Acid Inhibition of Osteoclastogenesis and Gene Expression of NF-κB p50 and c-Jun_Journal of Biomedical Engineering

Authors：

XUChunfeng , LIPeng , DONGWei , DINGShiyu , LIRen ,  QIMengchun , LIJinyuan

College of Stomatology, Hebei United University, Tangshan 063000, China;

Corresponding author：

QIMengchun, Email: qimengchun@163.com

Keywords：

osteoclast; zoledronate acid; receptor activator for nuclear factor-κB ligand; nuclear factor κB p50; c-Jun

DOI：

10.7507/1001-5515.20140072

Video：

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In this study, the rescue effect of receptor activator for nuclear factor-κB ligand (RANKL) on zoledronate acid (ZOL) induced inhibition of osteoclastogenesis and gene expression of NF-κB p50 and c-Jun was investigated. Mice calvarial osteoblasts (OBs) were harvested and co-cultured with RAW264.7 cells and the cells were divided into 4 groups and received treatment with ZOL and RANKL, either single or combined. The formation of multi-nucleated osteoclast (OC) was examined and gene expression of NF-κB p50 and c-Jun was detected. Group B (ZOL) showed least multi-nucleated OC and resorption lacunae among the 4 groups (P<0.05 or P<0.01) and it was followed by group C (ZOL+RANKL). Group D (RANKL) showed highest OC and resorption lacunae while it was similar to Group A (control) (P>0.05). Gene expression of NF-κB p50 and c-Jun was the lowest in group B (P<0.05 or P<0.01) among the four groups and was significantly increased in group C when compared with group B (P<0.05). Group A and D showed highest gene expression and they were similar to each other (P>0.05). This study suggest that RANKL might partly rescue ZOL induced inhibition of osteoclastogenesis, and the effect of RANKL and ZOL on osteoclastogenesis may be mediated by NF-κB p50 and c-Jun.

Citation： XUChunfeng, LIPeng, DONGWei, DINGShiyu, LIRen, QIMengchun, LIJinyuan. The Rescue Effect of RANKL on Zoledronate Induced Acid Inhibition of Osteoclastogenesis and Gene Expression of NF-κB p50 and c-Jun. Journal of Biomedical Engineering, 2014, 31(2): 385-388. doi: 10.7507/1001-5515.20140072 Copy

1.	EDWARDS J R,WEIVODA M M.Osteoclasts:malefactors of disease and targets for treatment[J].Discov Med,2012,13(70):201-210.
2.	NEGISHI-KOGA T,TAKAYANAGI H.Ca²⁺-NFATc1 signaling is an essential axis of osteoclast differentiation[J].Immunol Rev,2009,231(1):241-256.
3.	COXON F P,THOMPSON K,ROGERS M J.Recent advances in understanding the mechanism of action of bisphosphonates[J].Curr Opin Pharmacol,2006,6(3):307-312.
4.	戚孟春,胡静,邹淑娟,等.大鼠骨髓间充质干细胞和颅骨成骨细胞在张应力下细胞骨架的改变[J].华西口腔医学杂志,2005,23(2):110-112,121.
5.	GOHDA J,AKIYAMA T,KOGA T,et al.RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis[J].EMBO J,2005,24(4):790-799.
6.	BOYCE B F,YAO Z,XING L.Functions of nuclear factor kappaB in bone[J].Ann N Y Acad Sci,2010,1192:367-375.
7.	FRANZOSO G,CARLSON L,XING L,et al.Requirement for NF-kappaB in osteoclast and B-cell development[J].Genes Dev,1997,11(24):3482-3496.
8.	IOTSOVA V,CAAMANO J,LOY J,et al.Osteopetrosis in mice lacking NF-κB1 and NF-κB2[J].Nat Med,1997,3:1285-1289.
9.	YAMASHITA T,YAO Z,LI F,et al.NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1[J].J Biol Chem,2007,282(25):18245-18253.
10.	DAVID J P,SABAPATHY K,HOFFMANN O,et al.JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and-independent mechanisms[J].J Cell Sci,2002,115(Pt 22):4317-4325.
11.	IKEDA F,NISHIMURA R,MATSUBARA T,et al.Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation[J].J Clin Invest,2004,114(4):475-484.
12.	CHENG B,LI J,DU J,et al.Ginsenoside Rb1 inhibits osteoclastogenesis by modulating NF-κB and MAPKs pathways[J].Food Chem Toxicol,2012,50(5):1610-1615.
13.	SUTHERLAND K A,ROGERS H L,TOSH D,et al.RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro[J].Arthritis Res Ther,2009,11(2):R58.

1. EDWARDS J R,WEIVODA M M.Osteoclasts:malefactors of disease and targets for treatment[J].Discov Med,2012,13(70):201-210.
2. NEGISHI-KOGA T,TAKAYANAGI H.Ca²⁺-NFATc1 signaling is an essential axis of osteoclast differentiation[J].Immunol Rev,2009,231(1):241-256.
3. COXON F P,THOMPSON K,ROGERS M J.Recent advances in understanding the mechanism of action of bisphosphonates[J].Curr Opin Pharmacol,2006,6(3):307-312.
4. 戚孟春,胡静,邹淑娟,等.大鼠骨髓间充质干细胞和颅骨成骨细胞在张应力下细胞骨架的改变[J].华西口腔医学杂志,2005,23(2):110-112,121.
5. GOHDA J,AKIYAMA T,KOGA T,et al.RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis[J].EMBO J,2005,24(4):790-799.
6. BOYCE B F,YAO Z,XING L.Functions of nuclear factor kappaB in bone[J].Ann N Y Acad Sci,2010,1192:367-375.
7. FRANZOSO G,CARLSON L,XING L,et al.Requirement for NF-kappaB in osteoclast and B-cell development[J].Genes Dev,1997,11(24):3482-3496.
8. IOTSOVA V,CAAMANO J,LOY J,et al.Osteopetrosis in mice lacking NF-κB1 and NF-κB2[J].Nat Med,1997,3:1285-1289.
9. YAMASHITA T,YAO Z,LI F,et al.NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1[J].J Biol Chem,2007,282(25):18245-18253.
10. DAVID J P,SABAPATHY K,HOFFMANN O,et al.JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and-independent mechanisms[J].J Cell Sci,2002,115(Pt 22):4317-4325.
11. IKEDA F,NISHIMURA R,MATSUBARA T,et al.Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation[J].J Clin Invest,2004,114(4):475-484.
12. CHENG B,LI J,DU J,et al.Ginsenoside Rb1 inhibits osteoclastogenesis by modulating NF-κB and MAPKs pathways[J].Food Chem Toxicol,2012,50(5):1610-1615.
13. SUTHERLAND K A,ROGERS H L,TOSH D,et al.RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro[J].Arthritis Res Ther,2009,11(2):R58.

Journal of Biomedical Engineering

The Rescue Effect of RANKL on Zoledronate Induced Acid Inhibition of Osteoclastogenesis and Gene Expression of NF-κB p50 and c-Jun

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