Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing

References

Argetsinger, L.S., Campbell, G.S., Yang, X., Witthuhn, B.A., Silvennoinen, O., Ihle, J.N., and Carter-Su, C. (1993). Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell 74, 237–244.10.1016/0092-8674(93)90415-MSuche in Google Scholar

Brooks, A.J., Dai, W., O’Mara, M.L., Abankwa, D., Chhabra, Y., Pelekanos, R.A., Gardon, O., Tunny, K.A., Blucher, K.M., Morton, C.J., et al. (2014). Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science 344, 1249783.10.1126/science.1249783Suche in Google Scholar

Carter-Su, C., Argetsinger, L.S., Campbell, G.S., Wang, X., Ihle, J., and Witthuhn, B. (1994). The identification of JAK2 tyrosine kinase as a signaling molecule for growth hormone. Proc. Soc. Exp. Biol. Med. 206, 210–215.10.3181/00379727-206-43744Suche in Google Scholar

Ceradini, D.J., Kulkarni, A.R., Callaghan, M.J., Tepper, O.M., Bastidas, N., Kleinman, M.E., Capla, J.M., Galiano, R.D., Levine, J.P., and Gurtner, G.C. (2004). Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat. Med. 10, 858–864.10.1038/nm1075Suche in Google Scholar

El-Adawi, H., Deng, L., Tramontano, A., Smith, S., Mascareno, E., Ganguly, K., Castillo, R., and El-Sherif, N. (2003). The functional role of the JAK-STAT pathway in post-infarction remodeling. Cardiovasc. Res. 57, 129–138.10.1016/S0008-6363(02)00614-4Suche in Google Scholar

Gorogh, T., Quabius, E.S., Georgitsis, A., Hoffmann, M., and Lippross, S. (2017). Sequential activation of the AKT pathway in human osteoblasts treated with Oscarvit: a bioactive product with positive effect both on skeletal pain and mineralization in osteoblasts. BMC Musculoskelet. Disord. 18, 500.10.1186/s12891-017-1860-2Suche in Google Scholar

Hung, S.P., Ho, J.H., Shih, Y.R., Lo, T., and Lee, O.K. (2012). Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells. J. Orthop. Res. 30, 260–266.10.1002/jor.21517Suche in Google Scholar

Ishihara, K. and Hirano, T. (2002). Molecular basis of the cell specificity of cytokine action. Biochim. Biophys. Acta Mol. Cell. Res. 1592, 281–296.10.1016/S0167-4889(02)00321-XSuche in Google Scholar

Itoh, S., Udagawa, N., Takahashi, N., Yoshitake, F., Narita, H., Ebisu, S., and Ishihara, K. (2006). A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation. Bone 39, 505–512.10.1016/j.bone.2006.02.074Suche in Google Scholar

Keramaris, N.C., Calori, G.M., Nikolaou, V.S., Schemitsch, E.H., and Giannoudis, P.V. (2008). Fracture vascularity and bone healing: a systematic review of the role of VEGF. Injury 39 (Suppl. 2), S45–57.10.1016/S0020-1383(08)70015-9Suche in Google Scholar

Kitaori, T., Ito, H., Schwarz, E.A., Tsutsumi, R., Yoshitomi, H., Oishi, S., Nakano, M., Fujii, N., Nagasawa, T., and Nakamura, T. (2009). Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis Rheum. 60, 813–823.10.1002/art.24330Suche in Google Scholar

Kolar, P., Gaber, T., Perka, C., Duda, G.N., and Buttgereit, F. (2011). Human early fracture hematoma is characterized by inflammation and hypoxia. Clin. Orthop. Relat. Res. 469, 3118–3126.10.1007/s11999-011-1865-3Suche in Google Scholar

Kozawa, O., Otsuka, T., and Uematsu, T. (2002). Leukemia inhibitory factor enhances bFGF-induced IL-6 synthesis in osteoblasts: involvement of JAK2/STAT3. Cell Signal. 14, 311–315.10.1016/S0898-6568(01)00248-0Suche in Google Scholar

Levitzki, A. (1990). Tyrphostins – potential antiproliferative agents and novel molecular tools. Biochem. Pharmacol. 40, 913–918.10.1016/0006-2952(90)90474-YSuche in Google Scholar

Li, C.H., Zhao, J.X., Sun, L., Yao, Z.Q., Deng, X.L., Liu, R., and Liu, X.Y. (2013). AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis. Biochem. Biophys. Res. Commun. 435, 533–539.10.1016/j.bbrc.2013.04.084Suche in Google Scholar PubMed

Li, D.Q., Wan, Q.L., Pathak, J.L., and Li, Z.B. (2017a). Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis. J. Bone Miner. Metab. 35, 355–365.10.1007/s00774-016-0773-8Suche in Google Scholar PubMed

Li, K., Bao, H., Zhang, P., and Chen, L. (2017b). Inhibitory effect of AG490 on STAT3 signal transduction pathway in nasopharyngeal carcinoma cells. J. Coll. Physicians Surg. Pak. 27, 699–702.Suche in Google Scholar

Liu, K., Li, D., Huang, X., Lv, K., Ongodia, D., Zhu, L., Zhou, L., and Li, Z. (2013). A murine femoral segmental defect model for bone tissue engineering using a novel rigid internal fixation system. J. Surg. Res. 183, 493–502.10.1016/j.jss.2013.02.041Suche in Google Scholar PubMed

Maes, C., Coenegrachts, L., Stockmans, I., Daci, E., Luttun, A., Petryk, A., Gopalakrishnan, R., Moermans, K., Smets, N., Verfaillie, C.M., et al. (2006). Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair. J. Clin. Invest. 116, 1230–1242.10.1172/JCI26772Suche in Google Scholar PubMed PubMed Central

Manning, G., Whyte, D.B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002). The protein kinase complement of the human genome. Science 298, 1912–1934.10.1126/science.1075762Suche in Google Scholar PubMed

Marsell, R. and Einhorn, T.A. (2011). The biology of fracture healing. Injury 42, 551–555.10.1016/j.injury.2011.03.031Suche in Google Scholar PubMed PubMed Central

Matsuguchi, T., Chiba, N., Bandow, K., Kakimoto, K., Masuda, A., and Ohnishi, T. (2009). JNK activity is essential for Atf4 expression and late-stage osteoblast differentiation. J. Bone Miner. Res. 24, 398–410.10.1359/jbmr.081107Suche in Google Scholar PubMed

Meydan, N., Grunberger, T., Dadi, H., Shahar, M., Arpaia, E., Lapidot, Z., Leeder, J.S., Freedman, M., Cohen, A., Gazit, A., et al. (1996). Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature 379, 645–648.10.1038/379645a0Suche in Google Scholar PubMed

Nicolaidou, V., Wong, M.M., Redpath, A.N., Ersek, A., Baban, D.F., Williams, L.M., Cope, A.P., and Horwood, N.J. (2012). Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation. PLoS One 7, e39871.10.1371/journal.pone.0039871Suche in Google Scholar PubMed PubMed Central

Ohlsson, C., Bengtsson, B.A., Isaksson, O.G., Andreassen, T.T., and Slootweg, M.C. (1998). Growth hormone and bone. Endocr. Rev. 19, 55–79.10.1210/edrv.19.1.0324Suche in Google Scholar PubMed

Ortuno, M.J., Ruiz-Gaspa, S., Rodriguez-Carballo, E., Susperregui, A.R., Bartrons, R., Rosa, J.L., and Ventura, F. (2010). p38 regulates expression of osteoblast-specific genes by phosphorylation of osterix. J. Biol. Chem. 285, 31985–31994.10.1074/jbc.M110.123612Suche in Google Scholar PubMed PubMed Central

Ouyang, N., Zhang, P., Fu, R., Shen, G., Jiang, L., and Fang, B. (2018). Mechanical strain promotes osteogenic differentiation of bone mesenchymal stem cells from ovariectomized rats via the phosphoinositide 3kinase/Akt signaling pathway. Mol. Med. Rep. 17, 1855–1862.10.3892/mmr.2017.8030Suche in Google Scholar

Park, J.S., Lee, J., Lim, M.A., Kim, E.K., Kim, S.M., Ryu, J.G., Lee, J.H., Kwok, S.K., Park, K.S., Kim, H.Y., et al. (2014). JAK2-STAT3 blockade by AG490 suppresses autoimmune arthritis in mice via reciprocal regulation of regulatory T Cells and Th17 cells. J. Immunol. 192, 4417–4424.10.4049/jimmunol.1300514Suche in Google Scholar PubMed

Schipani, E., Maes, C., Carmeliet, G., and Semenza, G.L. (2009). Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J. Bone Miner. Res. 24, 1347–1353.10.1359/jbmr.090602Suche in Google Scholar PubMed PubMed Central

Wan, Q.L., Schoenmaker, T., Jansen, I.D.C., Bian, Z.A., de Vries, T.J., and Everts, V. (2016). Osteoblasts of calvaria induce higher numbers of osteoclasts than osteoblasts from long bone. Bone 86, 10–21.10.1016/j.bone.2016.02.010Suche in Google Scholar PubMed

Wang, X., Wang, Y., Gou, W., Lu, Q., Peng, J., and Lu, S. (2013). Role of mesenchymal stem cells in bone regeneration and fracture repair: a review. Int. Orthop. 37, 2491–2498.10.1007/s00264-013-2059-2Suche in Google Scholar PubMed PubMed Central

Xiao, G.Z., Jiang, D., Thomas, P., Benson, M.D., Guan, K.L., Karsenty, G., and Franceschi, R.T. (2000). MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J. Biol. Chem. 275, 4453–4459.10.1074/jbc.275.6.4453Suche in Google Scholar PubMed

Yu, X., Wan, Q., Cheng, G., Cheng, X., Zhang, J., Pathak, J.L., and Li, Z. (2018). CoCl2, a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway. Cell. Biol. Int. [Epub ahead of print]. doi: 10.1002/cbin.11017.10.1002/cbin.11017Suche in Google Scholar PubMed

Yue, R., Zhou, B.O., Shimada, I.S., Zhao, Z., and Morrison, S.J. (2016). Leptin receptor promotes adipogenesis and reduces osteogenesis by regulating mesenchymal stromal cells in adult bone marrow. Cell Stem Cell 18, 782–796.10.1016/j.stem.2016.02.015Suche in Google Scholar PubMed

Zhang, Q.B., Zhang, Z.Q., Fang, S.L., Liu, Y.R., Jiang, G., and Li, K.F. (2014). Effects of hypoxia on proliferation and osteogenic differentiation of periodontal ligament stem cells: an in vitro and in vivo study. Genet. Mol. Res. 13, 10204–10214.10.4238/2014.December.4.15Suche in Google Scholar PubMed

Zhao, Y., Song, T., Wang, W., Wang, J., He, J., Wu, N., Tang, M., He, B., and Luo, J. (2012). P38 and ERK1/2 MAPKs act in opposition to regulate BMP9-induced osteogenic differentiation of mesenchymal progenitor cells. PLoS One 7, e43383.10.1371/journal.pone.0043383Suche in Google Scholar PubMed PubMed Central