DOI QR코드

DOI QR Code

GP130 cytokines and bone remodelling in health and disease

  • Sims, Natalie A. (St Vincent's Institute, Australia and Department of Medicine at St. Vincent's Hospital, The University of Melbourne) ;
  • Walsh, Nicole C. (St Vincent's Institute, Australia and Department of Medicine at St. Vincent's Hospital, The University of Melbourne)
  • Received : 2010.07.15
  • Published : 2010.08.31

Abstract

Cytokines that bind to and signal through the gp130 co-receptor subunit include interleukin (IL)-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and ciliary neutrophic factor (CNTF). Apart from contributing to inflammation, gp130 signalling cytokines also function in the maintenance of bone homeostasis. Expression of each of these cytokines and their ligand-specific receptors is observed in bone and joint cells, and bone-active hormones and inflammatory cytokines regulate their expression. gp130 signalling cytokines have been shown to regulate the differentiation and activity of osteoblasts, osteoclasts and chondrocytes. Furthermore, cytokine and receptor specific gene-knockout mouse models have identified distinct roles for each of these cytokines in regulating bone resorption, bone formation and bone growth. This review will discuss the current models of paracrine and endocrine actions of gp130-signalling cytokines in bone remodelling and growth, as well as their impact in pathologic bone remodelling evident in periodontal disease, rheumatoid arthritis, spondylarthropathies and osteoarthritis.

References

  1. Bravo, J. and Heath, J. K. (2000) Receptor recognition by gp130 cytokines. Embo J. 19, 2399-2411. https://doi.org/10.1093/emboj/19.11.2399
  2. Yamasaki, K., Taga, T., Hirata, Y., Yawata, H., Kawanishi, Y., Seed, B., Taniguchi, T., Hirano, T. and Kishimoto, T. (1988) Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science 241, 825-828. https://doi.org/10.1126/science.3136546
  3. Hilton, D. J., Hilton, A. A., Raicevic, A., Rakar, S., Harrison-Smith, M., Gough, N. M., Begley, C. G., Metcalf, D., Nicola, N. A. and Willson, T. A. (1994) Cloning of a murine IL-11 receptor alpha-chain; requirement for gp130 for high affinity binding and signal transduction. Embo J. 13, 4765-4775.
  4. Elson, G. C., Lelievre, E., Guillet, C., Chevalier, S., Plun-Favreau, H., Froger, J., Suard, I., de Coignac, A. B., Delneste, Y., Bonnefoy, J. Y., Gauchat, J. F. and Gascan, H. (2000) CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat. Neurosci. 3, 867-872. https://doi.org/10.1038/78765
  5. Plun-Favreau, H., Elson, G., Chabbert, M., Froger, J., deLapeyriere, O., Lelievre, E., Guillet, C., Hermann, J., Gauchat, J. F., Gascan, H. and Chevalier, S. (2001) The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine. Embo J. 20, 1692-1703. https://doi.org/10.1093/emboj/20.7.1692
  6. Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T. and Kishimoto, T. (1990) Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63, 1149-1157. https://doi.org/10.1016/0092-8674(90)90411-7
  7. Gearing, D. P., Thut, C. J., VandeBos, T., Gimpel, S. D., Delaney, P. B., King, J., Price, V., Cosman, D. and Beckmann, M. P. (1991) Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. Embo J. 10, 2839-2848.
  8. Mosley, B., De Imus, C., Friend, D., Boiani, N., Thoma, B., Park, L. S. and Cosman, D. (1996) Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation. J. Biol. Chem. 271, 32635-32643 https://doi.org/10.1074/jbc.271.51.32635
  9. Lindberg, R. A., Juan, T. S., Welcher, A. A., Sun, Y., Cupples, R., Guthrie, B. and Fletcher, F. A. (1998) Cloning and characterization of a specific receptor for mouse oncostatin M. Mol. Cell Biol. 18, 3357-3367. https://doi.org/10.1128/MCB.18.6.3357
  10. Pflanz, S., Timans, J. C., Cheung, J., Rosales, R., Kanzler, H., Gilbert, J., Hibbert, L., Churakova, T., Travis, M., Vaisberg, E., Blumenschein, W. M., Mattson, J. D., Wagner, J. L., To, W., Zurawski, S., McClanahan, T. K., Gorman, D. M., Bazan, J. F., de Waal Malefyt, R., Rennick, D. and Kastelein, R. A. (2002) IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 16, 779-790. https://doi.org/10.1016/S1074-7613(02)00324-2
  11. Hashimoto, Y., Kurita, M., Aiso, S., Nishimoto, I. and Matsuoka, M. (2009) Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130. Mol. Biol. Cell 20, 2864-2873. https://doi.org/10.1091/mbc.E09-02-0168
  12. Sims, N. A. and Gooi, J. H. (2008) Bone remodeling: multiple cellular interactions required for coupling of bone formation and resorption. Semin. Cell Dev. Biol. 19, 444-451. https://doi.org/10.1016/j.semcdb.2008.07.016
  13. Martin, T. J. and Sims, N. A. (2009) Bone remodeling: cellular and molecular events; in The Skeletal System, Pourquie, O. (ed.), pp. 297-316, Cold Spring Harbor Press, New York, USA.
  14. Walker, E. C., McGregor, N. E., Poulton, I. J., Pompolo, S., Allan, E. H., Quinn, J. M., Gillespie, M. T., Martin, T. J. and Sims, N. A. (2008) Cardiotrophin-1 is an osteoclast-derived stimulus of bone formation required for normal bone remodeling. J. Bone Miner Res. 23, 2025-2032. https://doi.org/10.1359/jbmr.080706
  15. Pederson, L., Ruan, M., Westendorf, J. J., Khosla, S. and Oursler, M. J. (2008) Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc. Natl. Acad. Sci. U.S.A. 105, 20764-20769. https://doi.org/10.1073/pnas.0805133106
  16. van Bezooijen, R. L., ten Dijke, P., Papapoulos, S. E. and Lowik, C. W. (2005) SOST/sclerostin, an osteocyte- derived negative regulator of bone formation. Cytokine Growth Factor Rev. 16, 319-327. https://doi.org/10.1016/j.cytogfr.2005.02.005
  17. Kogianni, G., Mann, V. and Noble, B. S. (2008) Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localised bone destruction. J. Bone Miner Res. 23, 915-927. https://doi.org/10.1359/jbmr.080207
  18. Laaksovirta, H., Soinila, S., Hukkanen, V., Roytta, M. and Soilu-Hanninen, M. (2008) Serum level of CNTF is elevated in patients with amyotrophic lateral sclerosis and correlates with site of disease onset. Eur. J. Neurol. 15, 355-359. https://doi.org/10.1111/j.1468-1331.2008.02080.x
  19. Waring, P., Wycherley, K., Cary, D., Nicola, N. and Metcalf, D. (1992) Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids. J. Clin. Invest 90, 2031-2037. https://doi.org/10.1172/JCI116083
  20. Talwar, S., Downie, P. F., Squire, I. B., Barnett, D. B., Davies, J. D. and Ng, L. L. (1999) An immunoluminometric assay for cardiotrophin-1: a newly identified cytokine is present in normal human plasma and is increased in heart failure. Biochem. Biophys. Res. Commun. 261, 567-571. https://doi.org/10.1006/bbrc.1999.1084
  21. Daynes, R. A., Araneo, B. A., Ershler, W. B., Maloney, C., Li, G. Z. and Ryu, S. Y. (1993) Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. J. Immunol. 150, 5219-5230.
  22. Romas, E., Udagawa, N., Zhou, H., Tamura, T., Saito, M., Taga, T., Hilton, D. J., Suda, T., Ng, K. W. and Martin, T. J. (1996) The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures. J. Exp. Med. 183, 2581-2591. https://doi.org/10.1084/jem.183.6.2581
  23. Manolagas, S. C. (1998) The role of IL-6 type cytokines and their receptors in bone. Ann. N. Y. Acad. Sci. 840, 194-204. https://doi.org/10.1111/j.1749-6632.1998.tb09563.x
  24. Greenfield, E. M., Shaw, S. M., Gornik, S. A. and Banks, M. A. (1995) Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption. J. Clin. Invest. 96, 1238-1244. https://doi.org/10.1172/JCI118157
  25. Liang, J. D., Hock, J. M., Sandusky, G. E., Santerre, R. F. and Onyia, J. E. (1999) Immunohistochemical localization of selected early response genes expressed in trabecular bone of young rats given hPTH 1-34. Calcif. Tissue Int. 65, 369-373. https://doi.org/10.1007/s002239900715
  26. Tamura, T., Udagawa, N., Takahashi, N., Miyaura, C., Tanaka, S., Yamada, Y., Koishihara, Y., Ohsugi, Y., Kumaki, K., Taga, T., Kishimoto, T. and Suda, T. (1993) Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proc. Natl. Acad. Sci. U.S.A. 90, 11924-11928. https://doi.org/10.1073/pnas.90.24.11924
  27. Richards, C. D., Langdon, C., Deschamps, P., Pennica, D. and Shaughnessy, S. G. (2000) Stimulation of osteoclast differentiation in vitro by mouse oncostatin M, leukaemia inhibitory factor, cardiotrophin-1 and interleukin 6: synergy with dexamethasone. Cytokine 12, 613-621. https://doi.org/10.1006/cyto.1999.0635
  28. McGregor, N. E., Poulton, I. J., Walker, E. C., Pompolo, S., Quinn, J. M., Martin, T. J. and Sims, N. A. (2010) Ciliary neurotrophic factor inhibits bone formation and plays a sex-specific role in bone growth and remodeling. Calcif Tissue Int. 86, 261-270. https://doi.org/10.1007/s00223-010-9337-4
  29. Horwood, N. J., Elliott, J., Martin, T. J. and Gillespie, M. T. (1998) Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139, 4743-4746. https://doi.org/10.1210/en.139.11.4743
  30. Fu, Q., Manolagas, S. C. and O'Brien, C. A. (2006) Parathyroid hormone controls receptor activator of NFkappaB ligand gene expression via a distant transcriptional enhancer. Mol. Cell Biol. 26, 6453-6468. https://doi.org/10.1128/MCB.00356-06
  31. Atkins, G. J., Haynes, D. R., Geary, S. M., Loric, M., Crotti, T. N. and Findlay, D. M. (2000) Coordinated cytokine expression by stromal and hematopoietic cells during human osteoclast formation. Bone 26, 653-661. https://doi.org/10.1016/S8756-3282(00)00280-5
  32. Shin, H. I., Divieti, P., Sims, N. A., Kobayashi, T., Miao, D., Karaplis, A. C., Baron, R., Bringhurst, R. and Kronenberg, H. M. (2004) Gp130-mediated signaling is necessary for normal osteoblastic function in vivo and in vitro. Endocrinology 145, 1376-1385. https://doi.org/10.1210/en.2003-0839
  33. Girasole, G., Passeri, G., Jilka, R. L. and Manolagas, S. C. (1994) Interleukin-11: a new cytokine critical for osteoclast development. J. Clin. Invest. 93, 1516-1524. https://doi.org/10.1172/JCI117130
  34. Gorny, G., Shaw, A. and Oursler, M. J. (2004) IL-6, LIF, and TNF-alpha regulation of GM-CSF inhibition of osteoclastogenesis in vitro. Exp. Cell Res. 294, 149-158. https://doi.org/10.1016/j.yexcr.2003.11.009
  35. Sims, N. A., Jenkins, B. J., Quinn, J. M., Nakamura, A., Glatt, M., Gillespie, M. T., Ernst, M. and Martin, T. J. (2004) Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways. J. Clin. Invest 113, 379-389. https://doi.org/10.1172/JCI19872
  36. Sims, N. A., Jenkins, B. J., Nakamura, A., Quinn, J. M., Li, R., Gillespie, M. T., Ernst, M., Robb, L. and Martin, T. J. (2005) Interleukin-11 receptor signaling is required for normal bone remodeling. J. Bone Miner Res. 20, 1093-1102. https://doi.org/10.1359/JBMR.050209
  37. Kamiya, S., Nakamura, C., Fukawa, T., Ono, K., Ohwaki, T., Yoshimoto, T. and Wada, S. (2007) Effects of IL-23 and IL-27 on osteoblasts and osteoclasts: inhibitory effects on osteoclast differentiation. J. Bone Miner Metab. 25, 277-285. https://doi.org/10.1007/s00774-007-0766-8
  38. Kawasaki, K., Gao, Y. H., Yokose, S., Kaji, Y., Nakamura, T., Suda, T., Yoshida, K., Taga, T., Kishimoto, T., Kataoka, H., Yuasa, T., Norimatsu, H. and Yamaguchi, A. (1997) Osteoclasts are present in gp130-deficient mice. Endocrinology 138, 4959-4965. https://doi.org/10.1210/en.138.11.4959
  39. Poli, V., Balena, R., Fattori, E., Markatos, A., Yamamoto, M., Tanaka, H., Ciliberto, G., Rodan, G. A. and Costantini, F. (1994) Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. Embo J. 13, 1189-1196.
  40. Grey, A., Mitnick, M. A., Masiukiewicz, U., Sun, B. H., Rudikoff, S., Jilka, R. L., Manolagas, S. C. and Insogna, K. (1999) A role for interleukin-6 in parathyroid hormone-induced bone resorption in vivo. Endocrinology 140, 4683-4690. https://doi.org/10.1210/en.140.10.4683
  41. Bozec, A., Bakiri, L., Hoebertz, A., Eferl, R., Schilling, A. F., Komnenovic, V., Scheuch, H., Priemel, M., Stewart, C. L., Amling, M. and Wagner, E. F. (2008) Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia. Nature 454, 221-225. https://doi.org/10.1038/nature07019
  42. Ware, C. B., Horowitz, M. C., Renshaw, B. R., Hunt, J. S., Liggitt, D., Koblar, S. A., Gliniak, B. C., McKenna, H. J., Papayannopoulou, T., Thoma, B., Cheng, L., Donovan, P. J., Peschon, J. J., Bartlett, P. F., Willis, C. R., Wright, B. D., Carpenter, M. K., Davison, B. L. and Gearing, D. P. (1995) Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Development 121, 1283-1299.
  43. Walker, E. C., McGregor, N. E., Poulton, I. J., Solano, M., Pompolo, S., Fernandes, T. J., Constable, M. J., Nicholson, G. C., Zhang, J. G., Nicola, N. A., Gillespie, M. T., Martin, T. J. and Sims, N. A. (2010) Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. J. Clin. Invest 120, 582-592. https://doi.org/10.1172/JCI40568
  44. Bellido, T., Borba, V. Z., Roberson, P. and Manolagas, S. C. (1997) Activation of the Janus kinase/STAT (signal transducer and activator of transcription) signal transduction pathway by interleukin-6-type cytokines promotes osteoblast differentiation. Endocrinology 138, 3666-3676. https://doi.org/10.1210/en.138.9.3666
  45. Kitamura, H., Kawata, H., Takahashi, F., Higuchi, Y., Furuichi, T. and Ohkawa, H. (1995) Bone marrow neutrophilia and suppressed bone turnover in human interleukin-6 transgenic mice. A cellular relationship among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in bone marrow. Am. J. Pathol. 147, 1682-1692.
  46. De Benedetti, F., Rucci, N., Del Fattore, A., Peruzzi, B., Paro, R., Longo, M., Vivarelli, M., Muratori, F., Berni, S., Ballanti, P., Ferrari, S. and Teti, A. (2006) Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis. Rheum. 54, 3551-3563. https://doi.org/10.1002/art.22175
  47. Li, X., Ominsky, M. S., Warmington, K. S., Morony, S., Gong, J., Cao, J., Gao, Y., Shalhoub, V., Tipton, B., Haldankar, R., Chen, Q., Winters, A., Boone, T., Geng, Z., Niu, Q. T., Ke, H. Z., Kostenuik, P. J., Simonet, W. S., Lacey, D. L. and Paszty, C. (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J. Bone Miner Res. 24, 578-588. https://doi.org/10.1359/jbmr.081206
  48. Keller, H. and Kneissel, M. (2005) SOST is a target gene for PTH in bone. Bone 37, 148-158. https://doi.org/10.1016/j.bone.2005.03.018
  49. Robling, A. G., Bellido, T. and Turner, C. H. (2006) Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J. Musculoskelet Neuronal Interact 6, 354.
  50. Jenkins, B. J., Grail, D., Inglese, M., Quilici, C., Bozinovski, S., Wong, P. and Ernst, M. (2004) Imbalanced gp130-dependent signaling in macrophages alters macrophage colony-stimulating factor responsiveness via regulation of c-fms expression. Mol. Cell Biol. 24, 1453-1463. https://doi.org/10.1128/MCB.24.4.1453-1463.2004
  51. Dagoneau, N., Scheffer, D., Huber, C., Al-Gazali, L. I., Di Rocco, M., Godard, A., Martinovic, J., Raas-Rothschild, A., Sigaudy, S., Unger, S., Nicole, S., Fontaine, B., Taupin, J. L., Moreau, J. F., Superti-Furga, A., Le Merrer, M., Bonaventure, J., Munnich, A., Legeai-Mallet, L. and Cormier-Daire, V. (2004) Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome. Am. J. Hum. Genet. 74, 298-305. https://doi.org/10.1086/381715
  52. Sims, N. A. (2009) gp130 signaling in bone cell biology: multiple roles revealed by analysis of genetically altered mice. Mol. Cell Endocrinol. 310, 30-39. https://doi.org/10.1016/j.mce.2008.08.025
  53. Qi, L., Zhang, C., van Dam, R. M. and Hu, F. B. (2007) Interleukin-6 genetic variability and adiposity: associations in two prospective cohorts and systematic review in 26,944 individuals. J. Clin. Endocrinol. Metab. 92, 3618-3625. https://doi.org/10.1210/jc.2007-0877
  54. Takacs, I., Koller, D. L., Peacock, M., Christian, J. C., Evans, W. E., Hui, S. L., Conneally, P. M., Johnston, C. C., Jr., Foroud, T. and Econs, M. J. (2000) Sib pair linkage and association studies between bone mineral density and the interleukin-6 gene locus. Bone 27, 169-173. https://doi.org/10.1016/S8756-3282(00)00296-9
  55. Tsukamoto, K., Yoshida, H., Watanabe, S., Suzuki, T., Miyao, M., Hosoi, T., Orimo, H. and Emi, M. (1999) Association of radial bone mineral density with CA repeat polymorphism at the interleukin 6 locus in postmenopausal Japanese women. J. Hum. Genet. 44, 148-151. https://doi.org/10.1007/s100380050132
  56. Ogura, N., Shibata, Y., Kamino, Y., Matsuda, U., Hayakawa, M., Oikawa, T., Takiguchi, H., Izumi, H. and Abiko, Y. (1994) Stimulation of interleukin-6 production of periodontal ligament cells by Porphyromonas endodontalis lipopolysaccharide. Biochem. Med. Metab. Biol. 53, 130-136. https://doi.org/10.1006/bmmb.1994.1068
  57. Barkhordar, R. A., Hayashi, C. and Hussain, M. Z. (1999) Detection of interleukin-6 in human dental pulp and periapical lesions. Endod. Dent. Traumatol. 15, 26-27. https://doi.org/10.1111/j.1600-9657.1999.tb00744.x
  58. Johnson, R. B., Wood, N. and Serio, F. G. (2004) Interleukin-11 and IL-17 and the pathogenesis of periodontal disease. J. Periodontol. 75, 37-43. https://doi.org/10.1902/jop.2004.75.1.37
  59. Kawashima, N. and Stashenko, P. (1999) Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation. Arch. Oral. Biol. 44, 55-66. https://doi.org/10.1016/S0003-9969(98)00094-6
  60. Tsai, C. H., Huang, F. M. and Chang, Y. C. (2008) Immunohistochemical localization of oncostatin M in epithelialized apical periodontitis lesions. Int. Endod. J. 41, 772-776. https://doi.org/10.1111/j.1365-2591.2008.01430.x
  61. Lin, S. J., Chen, Y. L., Kuo, M. Y., Li, C. L. and Lu, H. K. (2005) Measurement of gp130 cytokines oncostatin M and IL-6 in gingival crevicular fluid of patients with chronic periodontitis. Cytokine 30, 160-167. https://doi.org/10.1016/j.cyto.2004.12.018
  62. Pradeep, A. R., S, T. M., Garima, G. and Raju, A. (2010) Serum levels of oncostatin M (a gp 130 cytokine): an inflammatory biomarker in periodontal disease. Biomarkers 15, 277-282. https://doi.org/10.3109/13547500903573209
  63. Gravallese, E. M., Harada, Y., Wang, J. T., Gorn, A. H., Thornhill, T. S. and Goldring, S. R. (1998) Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am. J. Pathol. 152, 943-951.
  64. Romas, E., Bakharevski, O., Hards, D. K., Kartsogiannis, V., Quinn, J. M., Ryan, P. F., Martin, T. J. and Gillespie, M. T. (2000) Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis. Arthritis Rheum 43, 821-826. https://doi.org/10.1002/1529-0131(200004)43:4<821::AID-ANR12>3.0.CO;2-T
  65. Scott, D. L. (2000) Prognostic factors in early rheumatoid arthritis. Rheumatology (Oxford) 39 (Suppl 1), 24-29. https://doi.org/10.1093/oxfordjournals.rheumatology.a031490
  66. Pettit, A. R., Walsh, N. C., Manning, C., Goldring, S. R. and Gravallese, E. M. (2006) RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis. Rheumatology (Oxford) 45, 1068-1076. https://doi.org/10.1093/rheumatology/kel045
  67. Horwood, N. J., Kartsogiannis, V., Quinn, J. M., Romas, E., Martin, T. J. and Gillespie, M. T. (1999) Activated T lymphocytes support osteoclast formation in vitro. Biochem. Biophys. Res. Commun. 265, 144-150. https://doi.org/10.1006/bbrc.1999.1623
  68. Crotti, T. N., Smith, M. D., Weedon, H., Ahern, M. J., Findlay, D. M., Kraan, M., Tak, P. P. and Haynes, D. R. (2002) Receptor activator NF-kappaB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Ann. Rheum. Dis. 61, 1047-1054. https://doi.org/10.1136/ard.61.12.1047
  69. 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. https://doi.org/10.1359/jbmr.090320
  70. Okamoto, H., Yamamura, M., Morita, Y., Harada, S., Makino, H. and Ota, Z. (1997) The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. Arthritis. Rheum. 40, 1096-1105. https://doi.org/10.1002/art.1780400614
  71. Kotake, S., Sato, K., Kim, K. J., Takahashi, N., Udagawa, N., Nakamura, I., Yamaguchi, A., Kishimoto, T., Suda, T. and Kashiwazaki, S. (1996) Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J. Bone Miner Res. 11, 88-95. https://doi.org/10.1002/jbmr.5650110113
  72. Nowell, M. A., Richards, P. J., Horiuchi, S., Yamamoto, N., Rose-John, S., Topley, N., Williams, A. S. and Jones, S. A. (2003) Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130. J. Immunol. 171, 3202-3209. https://doi.org/10.4049/jimmunol.171.6.3202
  73. Al-Awadhi, A., Olusi, S., Al-Zaid, N. and Prabha, K. (1999) Serum concentrations of interleukin 6, osteocalcin, intact parathyroid hormone, and markers of bone resorption in patients with rheumatoid arthritis. J. Rheumatol. 26, 1250-1256.
  74. Walsh, N. C., Crotti, T. N., Goldring, S. R. and Gravallese, E. M. (2005) Rheumatic diseases: the effects of inflammation on bone. Immunol. Rev. 208, 228-251. https://doi.org/10.1111/j.0105-2896.2005.00338.x
  75. Fonseca, J. E., Santos, M. J., Canhao, H. and Choy, E. (2009) Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun. Rev. 8, 538-542. https://doi.org/10.1016/j.autrev.2009.01.012
  76. Takagi, N., Mihara, M., Moriya, Y., Nishimoto, N., Yoshizaki, K., Kishimoto, T., Takeda, Y. and Ohsugi, Y. (1998) Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis. Arthritis. Rheum. 41, 2117-2121. https://doi.org/10.1002/1529-0131(199812)41:12<2117::AID-ART6>3.0.CO;2-P
  77. Kato, A., Matsuo, S., Takai, H., Uchiyama, Y., Mihara, M. and Suzuki, M. (2008) Early effects of tocilizumab on bone and bone marrow lesions in a collagen-induced arthritis monkey model. Exp. Mol. Pathol. 84, 262-270. https://doi.org/10.1016/j.yexmp.2008.03.003
  78. Jones, G., Sebba, A., Gu, J., Lowenstein, M. B., Calvo, A., Gomez-Reino, J. J., Siri, D. A., Tomsic, M., Alecock, E., Woodworth, T. and Genovese, M. C. (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: The AMBITION study. Ann. Rheum. Dis. 69, 88-96. https://doi.org/10.1136/ard.2008.105197
  79. Plater-Zyberk, C., Buckton, J., Thompson, S., Spaull, J., Zanders, E., Papworth, J. and Life, P. F. (2001) Amelioration of arthritis in two murine models using antibodies to oncostatin M. Arthritis. Rheum. 44, 2697-2702. https://doi.org/10.1002/1529-0131(200111)44:11<2697::AID-ART450>3.0.CO;2-#
  80. Field, M., Chu, C., Feldmann, M. and Maini, R. N. (1991) Interleukin-6 localisation in the synovial membrane in rheumatoid arthritis. Rheumatol. Int. 11, 45-50. https://doi.org/10.1007/BF00291144
  81. Chu, C. Q., Field, M., Allard, S., Abney, E., Feldmann, M. and Maini, R. N. (1992) Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. Br. J. Rheumatol. 31, 653-661. https://doi.org/10.1093/rheumatology/31.10.653
  82. Wong, P. K., Quinn, J. M., Sims, N. A., van Nieuwenhuijze, A., Campbell, I. K. and Wicks, I. P. (2006) Interleukin-6 modulates production of T lymphocytederived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis. Rheum. 54, 158-168. https://doi.org/10.1002/art.21537
  83. Mihara, M., Ohsugi, Y. and Kishimoto, T. (2009) Evidence for the role of Th17 cell inhibition in the prevention of autoimmune diseases by anti-interluekin-6 receptor antibody. Biofactors 35, 47-51. https://doi.org/10.1002/biof.9
  84. Fujimoto, M., Serada, S., Mihara, M., Uchiyama, Y., Yoshida, H., Koike, N., Ohsugi, Y., Nishikawa, T., Ripley, B., Kimura, A., Kishimoto, T. and Naka, T. (2008) Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses. Arthritis. Rheum. 58, 3710-3719. https://doi.org/10.1002/art.24126
  85. Benjamin, M., Moriggl, B., Brenner, E., Emery, P., McGonagle, D. and Redman, S. (2004) The "enthesis organ" concept: why enthesopathies may not present as focal insertional disorders. Arthritis. Rheum. 50, 3306-3313. https://doi.org/10.1002/art.20566
  86. McGonagle, D. (2005) Imaging the joint and enthesis: insights into pathogenesis of psoriatic arthritis. Ann. Rheum. Dis. 64 (Suppl 2), ii58-60. https://doi.org/10.1136/ard.2004.034264
  87. McGonagle, D., Lories, R. J., Tan, A. L. and Benjamin, M. (2007) The concept of a "synovio-entheseal complex" and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis. Rheum. 56, 2482-2491. https://doi.org/10.1002/art.22758
  88. Benjamin, M. and McGonagle, D. (2007) Histopathologic changes at "synovio-entheseal complexes" suggesting a novel mechanism for synovitis in osteoarthritis and spondylarthritis. Arthritis. Rheum. 56, 3601-3609. https://doi.org/10.1002/art.23078
  89. Lories, R. J., Derese, I. and Luyten, F. P. (2005) Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J. Clin. Invest. 115, 1571-1579. https://doi.org/10.1172/JCI23738
  90. Diarra, D., Stolina, M., Polzer, K., Zwerina, J., Ominsky, M. S., Dwyer, D., Korb, A., Smolen, J., Hoffmann, M., Scheinecker, C., van der Heide, D., Landewe, R., Lacey, D., Richards, W. G. and Schett, G. (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat. Med. 13, 156-163. https://doi.org/10.1038/nm1538
  91. Appel, H., Ruiz-Heiland, G., Listing, J., Zwerina, J., Herrmann, M., Mueller, R., Haibel, H., Baraliakos, X., Hempfing, A., Rudwaleit, M., Sieper, J. and Schett, G. (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis. Rheum. 60, 3257-3262. https://doi.org/10.1002/art.24888
  92. Partsch, G., Steiner, G., Leeb, B. F., Dunky, A., Broll, H. and Smolen, J. S. (1997) Highly increased levels of tumor necrosis factor-alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid. J. Rheumatol. 24, 518-523.
  93. Gratacos, J., Collado, A., Filella, X., Sanmarti, R., Canete, J., Llena, J., Molina, R., Ballesta, A. and Munoz-Gomez, J. (1994) Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br. J. Rheumatol. 33, 927-931. https://doi.org/10.1093/rheumatology/33.10.927
  94. Hayer, S., Niederreiter, B., Nagelreiter, I., Smolen, J. and Redlich, K. (2010) Interleukin 6 is not a crucial regulator in an animal model of tumour necrosis factor-mediated bilateral sacroiliitis. Ann. Rheum. Dis. 69, 1403-1406. https://doi.org/10.1136/ard.2010.129148
  95. Dieppe, P. A. and Lohmander, L. S. (2005) Pathogenesis and management of pain in osteoarthritis. Lancet 365, 965-973. https://doi.org/10.1016/S0140-6736(05)71086-2
  96. Sakao, K., Takahashi, K. A., Arai, Y., Saito, M., Honjo, K., Hiraoka, N., Asada, H., Shin-Ya, M., Imanishi, J., Mazda, O. and Kubo, T. (2009) Osteoblasts derived from osteophytes produce interleukin-6, interleukin-8, and matrix metalloproteinase-13 in osteoarthritis. J. Bone Miner Metab. 27, 412-423. https://doi.org/10.1007/s00774-009-0058-6
  97. Durigova, M., Roughley, P. J. and Mort, J. S. (2008) Mechanism of proteoglycan aggregate degradation in cartilage stimulated with oncostatin M. Osteoarthritis Cartilage 16, 98-104. https://doi.org/10.1016/j.joca.2007.05.002
  98. Langdon, C., Kerr, C., Hassen, M., Hara, T., Arsenault, A. L. and Richards, C. D. (2000) Murine oncostatin M stimulates mouse synovial fibroblasts in vitro and induces inflammation and destruction in mouse joints in vivo. Am. J. Pathol. 157, 1187-1196. https://doi.org/10.1016/S0002-9440(10)64634-2
  99. de Hooge, A. S., van de Loo, F. A., Bennink, M. B., de Jong, D. S., Arntz, O. J., Lubberts, E., Richards, C. D. and vandDen Berg, W. B. (2002) Adenoviral transfer of murine oncostatin M elicits periosteal bone apposition in knee joints of mice, despite synovial inflammation and up-regulated expression of interleukin-6 and receptor activator of nuclear factor-kappa B ligand. Am. J. Pathol. 160, 1733-1743. https://doi.org/10.1016/S0002-9440(10)61120-0
  100. Karsdal, M. A., Madsen, S. H., Christiansen, C., Henriksen, K., Fosang, A. J. and Sondergaard, B. C. (2008) Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity. Arthritis. Res. Ther. 10, R63. https://doi.org/10.1186/ar2434
  101. de Hooge, A. S., van de Loo, F. A., Bennink, M. B., Arntz, O. J., de Hooge, P. and van den Berg, W. B. (2005) Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging. Osteoarthritis. Cartilage. 13, 66-73. https://doi.org/10.1016/j.joca.2004.09.011
  102. Upadhyay, A., Sharma, G., Kivivuori, S., Raye, W. S., Zabihi, E., Carroll, G. J. and Jazayeri, J. A. (2009) Role of a LIF antagonist in LIF and OSM induced MMP-1, MMP-3, and TIMP-1 expression by primary articular chondrocytes. Cytokine 46, 332-338. https://doi.org/10.1016/j.cyto.2009.03.001
  103. Fan, Z., Bau, B., Yang, H. and Aigner, T. (2004) IL-1beta induction of IL-6 and LIF in normal articular human chondrocytes involves the ERK, p38 and NFkappaB signaling pathways. Cytokine 28, 17-24. https://doi.org/10.1016/j.cyto.2004.06.003
  104. Rowan, A. D., Koshy, P. J., Shingleton, W. D., Degnan, B. A., Heath, J. K., Vernallis, A. B., Spaull, J. R., Life, P. F., Hudson, K. and Cawston, T. E. (2001) Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis. Rheum. 44, 1620-1632. https://doi.org/10.1002/1529-0131(200107)44:7<1620::AID-ART285>3.0.CO;2-B
  105. Gao, Y., Morita, I., Maruo, N., Kubota, T., Murota, S. and Aso, T. (1998) Expression of IL-6 receptor and GP130 in mouse bone marrow cells during osteoclast differentiation. Bone 22, 487-493. https://doi.org/10.1016/S8756-3282(98)00040-4
  106. Allan, E. H., Hilton, D. J., Brown, M. A., Evely, R. S., Yumita, S., Metcalf, D., Gough, N. M., Ng, K. W., Nicola, N. A. and Martin, T. J. (1990) Osteoblasts display receptors for and responses to leukemia-inhibitory factor. J. Cell Physiol. 145, 110-119. https://doi.org/10.1002/jcp.1041450116
  107. Udagawa, N., Takahashi, N., Katagiri, T., Tamura, T., Wada, S., Findlay, D. M., Martin, T. J., Hirota, H., Taga, T., Kishimoto, T. and Suda, T. (1995) Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors. J. Exp. Med. 182, 1461-1468. https://doi.org/10.1084/jem.182.5.1461
  108. Bellido, T., Stahl, N., Farruggella, T. J., Borba, V., Yancopoulos, G. D. and Manolagas, S. C. (1996) Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells. J. Clin. Invest. 97, 431-437. https://doi.org/10.1172/JCI118432
  109. Dame, J. B. and Juul, S. E. (2000) The distribution of receptors for the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in the developing human fetus. Early Hum. Dev. 58, 25-39. https://doi.org/10.1016/S0378-3782(00)00064-5
  110. Legendre, F., Dudhia, J., Pujol, J. P. and Bogdanowicz, P. (2003) JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of SOX9 expression. J. Biol. Chem. 278, 2903-2912. https://doi.org/10.1074/jbc.M110773200
  111. Nowell, M. A., Richards, P. J., Fielding, C. A., Ognjanovic, S., Topley, N., Williams, A. S., Bryant-Greenwood, G. and Jones, S. A. (2006) Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis. Arthritis. Rheum. 54, 2084-2095. https://doi.org/10.1002/art.21942
  112. Hashizume, M., Hayakawa, N. and Mihara, M. (2008) IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-alpha and IL-17. Rheumatology (Oxford) 47, 1635-1640. https://doi.org/10.1093/rheumatology/ken363
  113. Wong, C., Chen, D., Tam, L., Li, E., Yin, Y. and Lam, C. (2010) Effects of inflammatory cytokine IL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res. Ther. 12, doi:10.1186/ar3067.
  114. Ishimi, Y., Miyaura, C., Jin, C. H., Akatsu, T., Abe, E., Nakamura, Y., Yamaguchi, A., Yoshiki, S., Matsuda, T., Hirano, T., Kishimoto, T. and Suda, T. (1990) IL-6 is produced by osteoblasts and induces bone resorption. J. Immunol. 145, 3297-3303.
  115. Ishimi, Y., Abe, E., Jin, C. H., Miyaura, C., Hong, M. H., Oshida, M., Kurosawa, H., Yamaguchi, Y., Tomida, M., Hozumi, M. and Suda, T. (1992) Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor): regulation of its production and possible roles in bone metabolism. J. Cell Physiol. 152, 71-78. https://doi.org/10.1002/jcp.1041520110
  116. Liu, F., Aubin, J. E. and Malaval, L. (2002) Expression of leukemia inhibitory factor (LIF)/interleukin-6 family cytokines and receptors during in vitro osteogenesis: differential regulation by dexamethasone and LIF. Bone 31, 212-219. https://doi.org/10.1016/S8756-3282(02)00806-2
  117. Guerne, P. A., Carson, D. A. and Lotz, M. (1990) IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J. Immunol. 144, 499-505.
  118. Maier, R., Ganu, V. and Lotz, M. (1993) Interleukin-11, an inducible cytokine in human articular chondrocytes and synoviocytes, stimulates the production of the tissue inhibitor of metalloproteinases. J. Biol. Chem. 268, 21527-21532.
  119. Grimaud, E., Blanchard, F., Charrier, C., Gouin, F., Redini, F. and Heymann, D. (2002) Leukaemia inhibitory factor (lif) is expressed in hypertrophic chondrocytes and vascular sprouts during osteogenesis. Cytokine 20, 224-230. https://doi.org/10.1006/cyto.2002.2002
  120. Sheng, Z., Pennica, D., Wood, W. I. and Chien, K. R. (1996) Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. Development 122, 419-428.

Cited by

  1. Hematopoiesis and bone remodeling vol.117, pp.21, 2011, https://doi.org/10.1182/blood-2011-03-344127
  2. Endothelin-1 induces oncostatin M expression in osteoarthritis osteoblasts by trans-activating the oncostatin M gene promoter via Ets-1 vol.13, pp.4, 2016, https://doi.org/10.3892/mmr.2016.4960
  3. The Enigmatic Cytokine Oncostatin M and Roles in Disease vol.2013, 2013, https://doi.org/10.1155/2013/512103
  4. Interleukin-4 and interleukin-13 inhibit the expression of leukemia inhibitory factor and interleukin-11 in fibroblasts vol.49, pp.4, 2012, https://doi.org/10.1016/j.molimm.2011.10.009
  5. Effects of Designer Hyper-Interleukin 11 (H11) on Hematopoiesis in Myelosuppressed Mice vol.11, pp.5, 2016, https://doi.org/10.1371/journal.pone.0154520
  6. Osteogenic Effects of Dedifferentiated Fat Cell Transplantation in Rabbit Models of Bone Defect and Ovariectomy-Induced Osteoporosis vol.19, pp.15-16, 2013, https://doi.org/10.1089/ten.tea.2012.0380
  7. The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblast-like MG-63 cells vol.48, pp.7, 2015, https://doi.org/10.1590/1414-431X20154494
  8. Inflammatory bone loss: pathogenesis and therapeutic intervention vol.11, pp.3, 2012, https://doi.org/10.1038/nrd3669
  9. gp130 in late osteoblasts and osteocytes is required for PTH-induced osteoblast differentiation vol.223, pp.2, 2014, https://doi.org/10.1530/JOE-14-0424
  10. Extensive Mannose Phosphorylation on Leukemia Inhibitory Factor (LIF) Controls Its Extracellular Levels by Multiple Mechanisms vol.286, pp.28, 2011, https://doi.org/10.1074/jbc.M111.221432
  11. Synovial IL-6 AS Inflammatory Marker in Periprosthetic Joint Infections vol.29, pp.6, 2014, https://doi.org/10.1016/j.arth.2014.01.014
  12. Contrasting roles of leukemia inhibitory factor in murine bone development and remodeling involve region-specific changes in vascularization vol.27, pp.3, 2012, https://doi.org/10.1002/jbmr.1485
  13. Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders vol.26, pp.5, 2015, https://doi.org/10.1016/j.cytogfr.2015.07.014
  14. A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro vol.12, pp.7, 2017, https://doi.org/10.1371/journal.pone.0181126
  15. Gomisin N Decreases Inflammatory Cytokine Production in Human Periodontal Ligament Cells vol.40, pp.2, 2017, https://doi.org/10.1007/s10753-016-0482-4
  16. IL-11 signaling as a therapeutic target for cancer vol.7, pp.4, 2015, https://doi.org/10.2217/imt.15.17
  17. Regulation of cortical and trabecular bone mass by communication between osteoblasts, osteocytes and osteoclasts vol.561, 2014, https://doi.org/10.1016/j.abb.2014.05.015
  18. Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL vol.11, pp.6, 2016, https://doi.org/10.1371/journal.pone.0156708
  19. Vascular effects of glycoprotein130 ligands — Part II: Biomarkers and therapeutic targets vol.57, pp.1, 2012, https://doi.org/10.1016/j.vph.2011.12.007
  20. Non-Linear Pattern Formation in Bone Growth and Architecture vol.5, 2015, https://doi.org/10.3389/fendo.2014.00239
  21. De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis vol.56, pp.5, 2011, https://doi.org/10.1038/jhg.2011.16
  22. Regulation of Sclerostin Expression by Paracrine and Endocrine Factors vol.10, pp.2, 2012, https://doi.org/10.1007/s12018-011-9121-7
  23. Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening vol.7, 2017, https://doi.org/10.1016/j.bonr.2017.07.003
  24. Discovering small molecules that inhibit adipogenesis and promote osteoblastogenesis: Unique screening and Oncostatin M-like activity vol.86, pp.1-2, 2013, https://doi.org/10.1016/j.diff.2013.07.005
  25. Histological Evidence of Increased Osteoclast Cell Number and Asymmetric Bone Resorption Activity in the Tibiae of Interleukin-6-Deficient Mice vol.62, pp.8, 2014, https://doi.org/10.1369/0022155414537830
  26. Myokines (muscle-derived cytokines and chemokines) including ciliary neurotrophic factor (CNTF) inhibit osteoblast differentiation vol.64, 2014, https://doi.org/10.1016/j.bone.2014.03.053
  27. Bone metastasis from breast cancer involves elevated IL-11 expression and the gp130/STAT3 pathway vol.30, pp.3, 2013, https://doi.org/10.1007/s12032-013-0634-4
  28. Enhancement of placenta growth factor expression by oncostatin M in human rheumatoid arthritis synovial fibroblasts vol.228, pp.5, 2013, https://doi.org/10.1002/jcp.24244
  29. Stüve-Wiedemann syndrome: LIFR and associated cytokines in clinical course and etiology vol.9, pp.1, 2014, https://doi.org/10.1186/1750-1172-9-34
  30. Mechanically Loaded Myotubes Affect Osteoclast Formation vol.94, pp.3, 2014, https://doi.org/10.1007/s00223-013-9813-8
  31. Oncostatin M acting via OSMR, augments the actions of IL-1 and TNF in synovial fibroblasts vol.68, pp.2, 2014, https://doi.org/10.1016/j.cyto.2014.04.001
  32. Coupling factors and exosomal packaging microRNAs involved in the regulation of bone remodelling 2017, https://doi.org/10.1111/brv.12353
  33. Lineage mapping and characterization of the native progenitor population in cellular allograft vol.13, pp.2, 2013, https://doi.org/10.1016/j.spinee.2012.11.017
  34. Interleukin-11 Drives Early Lung Inflammation during Mycobacterium tuberculosis Infection in Genetically Susceptible Mice vol.6, pp.7, 2011, https://doi.org/10.1371/journal.pone.0021878
  35. Murine Oncostatin M Acts via Leukemia Inhibitory Factor Receptor to Phosphorylate Signal Transducer and Activator of Transcription 3 (STAT3) but Not STAT1, an Effect That Protects Bone Mass vol.291, pp.41, 2016, https://doi.org/10.1074/jbc.M116.748483
  36. The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity vol.70, pp.13, 2013, https://doi.org/10.1007/s00018-012-1211-2
  37. The Effect of Recombinant Human Interleukin-6 on Osteogenic Differentiation and YKL-40 Expression in Human, Bone Marrow–Derived Mesenchymal Stem Cells vol.3, pp.1, 2014, https://doi.org/10.1089/biores.2013.0035
  38. MCP-1 Expression Is Specifically Regulated During Activation of Skeletal Repair and Remodeling vol.92, pp.6, 2013, https://doi.org/10.1007/s00223-013-9718-6
  39. Inhibition of Growth and Induction of Differentiation of SMMC-7721 Human Hepatocellular Carcinoma Cells by Oncostatin M vol.14, pp.2, 2013, https://doi.org/10.7314/APJCP.2013.14.2.747
  40. Osteoimmunology: oncostatin M as a pleiotropic regulator of bone formation and resorption in health and disease vol.3, 2014, https://doi.org/10.1038/bonekey.2014.22
  41. Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses vol.11, pp.1, 2014, https://doi.org/10.1186/s12985-014-0189-9
  42. Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure vol.5, pp.1, 2015, https://doi.org/10.1038/srep15529
  43. The Primary Function of gp130 Signaling in Osteoblasts Is To Maintain Bone Formation and Strength, Rather Than Promote Osteoclast Formation vol.29, pp.6, 2014, https://doi.org/10.1002/jbmr.2159
  44. Rosuvastatin inhibits spontaneous and IL-1β-induced interleukin-6 production from human cultured osteoblastic cells vol.80, pp.2, 2013, https://doi.org/10.1016/j.jbspin.2012.07.007
  45. Adipocytes and the Regulation of Bone Remodeling: A Balancing Act vol.94, pp.1, 2014, https://doi.org/10.1007/s00223-013-9807-6
  46. Rhizoma Dioscoreae Extract Protects against Alveolar Bone Loss in Ovariectomized Rats via microRNAs Regulation vol.7, pp.2, 2015, https://doi.org/10.3390/nu7021333
  47. Dangerous liaisons between interleukin-6 cytokine and toll-like receptor families: A potent combination in inflammation and cancer vol.24, pp.3, 2013, https://doi.org/10.1016/j.cytogfr.2013.03.007
  48. Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone vol.81, 2015, https://doi.org/10.1016/j.bone.2015.08.005
  49. Talking among Ourselves: Paracrine Control of Bone Formation within the Osteoblast Lineage vol.94, pp.1, 2014, https://doi.org/10.1007/s00223-013-9738-2
  50. Cells of the Immune System Orchestrate Changes in Bone Cell Function vol.94, pp.1, 2014, https://doi.org/10.1007/s00223-013-9764-0
  51. Adaptive Immune Response Inhibits Ectopic Mature Bone Formation Induced by BMSCs/BCP/Plasma Composite in Immune-Competent Mice vol.20, pp.21-22, 2014, https://doi.org/10.1089/ten.tea.2013.0633
  52. Stüve-Wiedemann syndrome and related bent bone dysplasias vol.82, pp.1, 2012, https://doi.org/10.1111/j.1399-0004.2012.01852.x
  53. Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model vol.14, pp.6, 2012, https://doi.org/10.1186/ar4107
  54. A designer hyper interleukin 11 (H11) is a biologically active cytokine vol.12, pp.1, 2012, https://doi.org/10.1186/1472-6750-12-8
  55. Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss vol.111, pp.16, 2014, https://doi.org/10.1073/pnas.1318859111
  56. The Landscape of Protein Biomarkers Proposed for Periodontal Disease: Markers with Functional Meaning vol.2014, 2014, https://doi.org/10.1155/2014/569632
  57. TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss vol.29, pp.11, 2015, https://doi.org/10.1096/fj.15-272559
  58. Protective effect of Rhizoma Dioscoreae extract against alveolar bone loss in ovariectomized rats via regulation of IL-6/STAT3 signaling vol.40, pp.5, 2017, https://doi.org/10.3892/ijmm.2017.3130
  59. Extracellular Matrix and Fibrocyte Accumulation in BALB/c Mouse Lung upon Transient Overexpression of Oncostatin M vol.8, pp.2, 2019, https://doi.org/10.3390/cells8020126