Browse > Article
http://dx.doi.org/10.14348/molcells.2015.2353

Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-κB Signaling  

Li, Aiguo (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University)
Yang, Libin (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University)
Geng, Xiaolin (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University)
Peng, Xingmei (Department of Oncology, The Third Affiliated Hospital of Xinxiang Medical University)
Lu, Tan (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University)
Deng, Yanjun (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University)
Dong, Yuzheng (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University)
Abstract
Rheumatoid arthritis is a chronic inflammatory disease that leads to bone and cartilage erosion. The inhibition of osteoblast differentiation by the inflammatory factor TNF-${\alpha}$ is critical for the pathogenesis of rheumatoid arthritis. To modulate TNF-${\alpha}$ mediated inhibition of osteoblast differentiation is required to improve therapeutic efficacy of rheumatoid arthritis. Here, we explored the potential role of rocaglamide-A, a component of Aglaia plant, in osteoblast differentiation. Rocaglamide-A prevented TNF-${\alpha}$ mediated inhibition of osteoblast differentiation, and promoted osteoblast differentiation directly, in both C2C12 and primary mesenchymal stromal cells. Mechanistically, Rocaglamide-A inhibited the phosphorylation of NF-${\kappa}B$ component p65 protein and the accumulation of p65 in nucleus, which resulted in the diminished NF-${\kappa}B$ responsible transcriptional activity. Oppositely, overexpression of p65 reversed rocaglamide-A's protective effects on osteoblast differentiation. Collectively, rocaglamide-A protected and stimulated osteoblast differentiation via blocking NF-${\kappa}B$ pathway. It suggests that rocaglamide-A may be a good candidate to develop as therapeutic drug for rheumatoid arthritis associated bone loss diseases.
Keywords
NF-${\kappa}B$; osteoblast differentiation; rocaglamide-A; TNF-${\alpha}$;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Azuma, Y., Kaji, K., Katogi, R., Takeshita, S. and Kudo, A. (2000) Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts. J. Biol. Chem. 275, 4858-4864.   DOI
2 Baumann, B., Bohnenstengel, F., Siegmund, D., Wajant, H., Weber, C., Herr, I., Debatin, K.M., Proksch, P., and Wirth, T. (2002). Rocaglamide derivatives are potent inhibitors of NF-kappa B activation in T-cells. J. Biol. Chem. 277, 44791-44800.   DOI
3 Bohnenstengel, F.I., Steube, K.G., Meyer, C., Nugroho, B.W., Hung, P.D., Kiet, L.C., and Proksch, P. (1999). Structure activity relationships of antiproliferative rocaglamide derivatives from Aglaia species (Meliaceae). Z. Naturforsch. C 54, 55-60.
4 Canalis, E. (1987) Effects of tumor necrosis factor on bone formation in vitro. Endocrinology 121, 1596-1604.   DOI
5 Chang, J., Wang, Z., Tang, E., Fan, Z., McCauley, L., Franceschi, R., Guan, K., Krebsbach, P.H., and Wang, C.Y. (2009). Inhibition of osteoblastic bone formation by nuclear factor-kappaB. Nat. Med. 15, 682-689.   DOI
6 Chang, J., Liu, F., Lee, M., Wu, B., Ting, K., Zara, J.N., Soo, C., Al Hezaimi, K., Zou, W., Chen, X., et al. (2013). NF-kappaB inhibits osteogenic differentiation of mesenchymal stem cells by promoting beta-catenin degradation. Proc. Natl. Acad. Sci. USA 110, 9469-9474.   DOI
7 Collett, G.P. and Campbell, F.C. (2006) Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells. Carcinogenesis 27, 1285-1291.   DOI
8 Dreyer, M., Nugroho, B.W., Bohnenstengel, F.I., Ebel, R., Wray, V., Witte, L., Bringmann, G., Muhlbacher, J., Herold, M., Hung, P.D., et al. (2001). New insecticidal rocaglamide derivatives and related compounds from Aglaia oligophylla. J. Nat. Prod. 64, 415-420.   DOI
9 Goldring, S.R. and Gravallese, E.M. (2000) Pathogenesis of bone erosions in rheumatoid arthritis. Curr. Opin. Rheumatol 12, 195-199.   DOI
10 Huang, W., Yang, S., Shao, J. and Li, Y.P. (2007) Signaling and transcriptional regulation in osteoblast commitment and differentiation. Front. Biosci. 12, 3068-3092.   DOI
11 Lee, S.K., Cui, B., Mehta, R.R., Kinghorn, A.D., and Pezzuto, J.M. (1998). Cytostatic mechanism and antitumor potential of novel 1H-cyclopenta[b]benzofuran lignans isolated from Aglaia elliptica. Chem. Biol. Interact. 115, 215-228.   DOI
12 Kaneko, H., Arakawa, T., Mano, H., Kaneda, T., Ogasawara, A., Nakagawa, M., Toyama, Y., Yabe, Y., Kumegawa, M. and Hakeda, Y. (2000). Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. Bone 27, 479-486.   DOI
13 Karsenty, G., Kronenberg, H.M. and Settembre, C. (2009) Genetic control of bone formation. Annu. Rev. Cell Dev. Biol. 25, 629-648.   DOI
14 Kim, S., Salim, A.A., Swanson, S.M., and Kinghorn, A.D. (2006). Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy. Anticancer Agents Med. Chem. 6, 319-345.   DOI
15 Lee, H.L., Yi, T., Woo, K.M., Ryoo, H.M., Kim, G.S., and Baek, J.H. (2010). Msx2 mediates the inhibitory action of TNF-alpha on osteoblast differentiation. Exp. Mol. Med. 42, 437-445.   DOI
16 Li, Y.C., Ross, J., Scheppler, J.A., and Franza, B.R., Jr. (1991). An in vitro transcription analysis of early responses of the human immunodeficiency virus type 1 long terminal repeat to different transcriptional activators. Mol. Cell Biol. 11, 1883-1893.   DOI
17 Li, Y., Li, A., Strait, K., Zhang, H., Nanes, M.S., and Weitzmann, M.N. (2007). Endogenous TNFalpha lowers maximum peak bone mass and inhibits osteoblastic Smad activation through NF-kappaB. J. Bone Miner Res. 22, 646-655.   DOI
18 McInnes, I.B., and Schett, G. (2007). Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol. 7, 429-442.   DOI
19 Mukai, T., Otsuka, F., Otani, H., Yamashita, M., Takasugi, K., Inagaki, K., Yamamura, M. and Makino, H. (2007). TNF-alpha inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling. Biochem. Biophys. Res. Commun. 356, 1004-1010.   DOI
20 Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63.   DOI
21 Nanjundaiah, S.M., Astry, B. and Moudgil, K.D. (2013) Mediators of inflammation-induced bone damage in arthritis and their control by herbal products. Evid. Based Complement Alternat. Med. 2013, 518094.
22 Proksch, P., Giaisi, M., Treiber, M.K., Palfi, K., Merling, A., Spring, H., Krammer, P.H. and Li-Weber, M. (2005). Rocaglamide derivatives are immunosuppressive phytochemicals that target NF-AT activity in T cells. J. Immunol. 174, 7075-7084.   DOI
23 Redlich, K., Hayer, S., Ricci, R., David, J.P., Tohidast-Akrad, M., Kollias, G., Steiner, G., Smolen, J.S., Wagner, E.F. and Schett, G. (2002). Osteoclasts are essential for TNF-alpha-mediated joint destruction. J. Clin. Invest. 110, 1419-1427.   DOI
24 Smucker, J.D., Rhee, J.M., Singh, K., Yoon, S.T., and Heller, J.G. (2006). Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine. Spine 31, 2813-2819.   DOI
25 Stanford, C.M., Jacobson, P.A., Eanes, E.D., Lembke, L.A. and Midura, R.J. (1995) Rapidly forming apatitic mineral in an osteoblastic cell line (UMR 106-01 BSP). J. Biol. Chem. 270, 9420-9428.   DOI
26 Yamazaki, M., Fukushima, H., Shin, M., Katagiri, T., Doi, T., Takahashi, T. and Jimi, E. (2009) Tumor necrosis factor alpha represses bone morphogenetic protein (BMP) signaling by interfering with the DNA binding of Smads through the activation of NF-kappaB. J. Biol. Chem. 284, 35987-35995.   DOI
27 Steer, J.H., Kroeger, K.M., Abraham, L.J. and Joyce, D.A. (2000). Glucocorticoids suppress tumor necrosis factor-alpha expression by human monocytic THP-1 cells by suppressing transactivation through adjacent NF-kappa B and c-Jun-activating transcription factor-2 binding sites in the promoter. J. Biol. Chem. 275, 18432-18440.   DOI
28 Walsh, N.C., Reinwald, S., Manning, C.A., Condon, K.W., Iwata, K., Burr, D.B. and Gravallese, E.M. (2009). Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J. Bone Miner Res. 24, 1572-1585.   DOI
29 Wong, D.A., Kumar, A., Jatana, S., Ghiselli, G., and Wong, K. (2008). Neurologic impairment from ectopic bone in the lumbar canal: a potential complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2). Spine J. 8, 1011-1018.   DOI
30 Zaidi, M. (2007) Skeletal remodeling in health and disease. Nat. Med. 13, 791-801.   DOI
31 Zhu, J.Y., Giaisi, M., Kohler, R., Muller, W.W., Muhleisen, A., Proksch, P., Krammer, P.H. and Li-Weber, M. (2009). Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression. Cell Death Differ. 16, 1289-1299.   DOI
32 Zara, J.N., Siu, R.K., Zhang, X., Shen, J., Ngo, R., Lee, M., Li, W., Chiang, M., Chung, J., Kwak, J., et al. (2011). High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo. Tissue Eng. Part A 17, 1389-1399.   DOI