Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

Frontiers in Bioscience

Volumn 12, Issue 4, 2007, Pages 1450-1462

  Jiang, Jean Xin ^a   Siller Jackson, Arlene Janel ^a   Burra, Sirisha ^a  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34249827264     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/2159     Document Type: Article

References (187)

1. Bennett, M.V.L. & Goodenough, D.A. Gap junctions, electronic coupling, and intercellular communication. Neurosciences Res. Prog.Bull. 16, 373-486 (1978)
2. Bergoffen, J., Scherer, S.S., Wang, S., Scott, M.O., Bone, L.J., Paul, D.L., Chen, K., Lensch, M.W., Chance, P.F. & Fischbeck, K.H. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science 262, 2039-2042 (1993)
3. Britz-Cunningham, S.H., Shah, M.M., Zuppan, C.W. & Fletcher, W.H. Mutations of the connexin43 gap-junction gene in patients with heart malformations and defects of laterality. New Engl.J.Med. 332, 1323-1329 (1995)
4. Reaume, A.G., De Sousa, P.A., Kulkarni, S., Langille, B.L., Zhu, D., Davies, T.C., Juneja, S.C., Kidder, G.M. & Rossant, J. Cardiac malformation in neonatal mice lacking connexin43. Science 267, 1831-1834 (1995)
5. Simon, A.M., Goodenough, D.A., Li, E. & Paul, D.L. Female infertility in mice lacking connexin37. Nature (Land.) 385, 525-529 (1997)
6. Kelsell, D.P., Dunlop, J., Stevens, H.P., Lench, N.J., Liang, J.N., Parry, G., Mueller, R.F. & Leigh, I.M. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387, 80-83 (1997)
7. Gong, X., Li, E., Klier, G., Huang, Q., Wu, Y., Lei, H., Kumar, N.M., Horwitz, J. & Gilua, N.B. Disruption of alphas connexin gene leads to proteolysis and cataractogenesis in mice. Cell 91, 833-843 (1997)
8. Jiang, J.X., White, T.W. & Goodenough, D.A. Changes in connexin expression and distribution during chick lens development. Dev.Biol. 168, 649-661 (1995)
9. Eiberger, J., Degen, J., romualdi, A., Deutsch, U., Willecke, K. & Sohl, G. Connexin genes in the mouse and human genome. Cell Commun.Adhes. 8, 163-165 (2001)
10. Willecke, K., Eiberger, J., Degen, J., Eckardt, D., romualdi, A., Guldenagel, M., Deutsch, U. & Sohl, G. Structural and functional diversity of connexin genes in the mouse and human genome. Biol.Chem. 383, 725-737 (2002)
11. Saez, J.C., Berthoud, V.M., Branes, M.C., Martinez, A.D. & Beyer, E.C. Plasma membrane channels formed by connexins: their regulation and functions. Physiol.Rev. 83, 1359-1400 (2003)
12. Goodenough, D.A., Goliger, J.A. & Paul, D.L. Connexins, connexons, and intercellular communication. Annu.Rev.Biochem. 65, 475-502 (1996)
13. Schirrmacher, K., Schmiz, I., Winterhager, E., Traub, O., Bremmer, F., Jones, D. & Binbmann, D. Characterization of gap junctions between osteoblast-like cells in culture. Calcif. Tissue Int. 51, 285-290 (1992)
14. Civitelli, R., Beyer, E.C., Warlow, P.M., Roberson, A.J., Geist, S.T. & Steinberg, T.H. Connexin43 mediates direct intercellular communication in human osteoblastic cell networks. J.Clin.Invest. 1888-1896 (1993)
15. Edelson, E. Conduits for cell/cell communication. MOSAIC 21, 48-56 (1990)
16. Mason, D.J., Hillam, R. & Skerry, T.M. Constitutive in vivo mRNA expression by osteocytes of beta-actin, osteocalcin, connexin-43, IGF-1, c-fos and c-jun, but not TNF-alpha nor tartrate-resistant acid phosphatase. J.Bone Miner.Res. 11, 350-357 (1996)
17. Su, M., Borke, J.L., Donahue, H.J., Li, Z., Warshawsky, N.M., Russell, C.M. & Lewis, J.E. Expression of connexin 43 in rat mandibular bone and periodontal ligament (PDL) cells during experimental tooth movement. J.Dent Res 76, 1357-1366 (1997)
18. Chiba, H., Sawada, N., Oyamada, M., Kojima, T., Nomura, S., Ishii, S. & Mon, M. Relationship between the expression of the gap junction protein and osteoblast phenotype in a human osteoblastic cell line during cell proliferation. Cell Structure & Function 18, 419-426 (1993)
19. Yamaguchi, D.T., Ma, D., Lee, A., Huang, J. & Gruber, H.E. Isolation and characterization of gap junctions in the osteoblastic MC3T3-E1 cell line. J.Bone Miner.Res. 9, 791-803 (1994)
20. Cheng, B., Zhao, S., Luo, J., Sprague, E., Bonewald, L.F. & Jiang, J.X. Expression of functional gap junctions and regulation by fluid flow shear stress in osteocyte-like MLO-Y4 cells. J.Bone Miner.Res. 16, 249-259 (2001)
21. Thi, M.M., Kojima, T., Cowin, S.C., Weinbaum, S. & Spray, D.C. Fluid flow stress remodels expression and function of junctional proteins in cultured bone cells. Am.J.Physiol.(Cell Physiol.) 284, C389-C403 (2003)
22. Donahue, H.J., Guilak, F., Vander Molen, M.A., Mcleod, K.J., Rubin, C.T., Grande, D.A. & Brink, P.R. Chondrocytes isolated from mature articular acrtilage retain the capacity to form functional gap junctions. J.Bone Miner.Res. 10, 1359-1364 (1995)
23. Schwab, W., Hofer, A. & Kasper, M. Immunohistochemical distribution of connexin 43 in the cartilage of rats and mice. Histochem.J. 30, 413-419 (1998)
24. Chi, S.S., Rattner, J.B. & Matyas, J.R. Communication between paired chondrocytes in the superficial zone of articular cartilage. J.Anat. 205, 363-370 (2004)
25. Koval, M., Harley, J.E., Hinck, E. & Steinberg, T.H. Connexin46 is retained as monomer in a trans-golgi compartment of osteoblastic cells. J.Cell Biol. 137, 847-857 (1997)
26. Steinberg, T.H., Civitelli, R., Geist, S.T., Robertson, A.J., Hick, E., Veenstra, R.D., Wang, H.Z., Warlow, P.M., Westphale, E.M., Laing, J.G. & et al. Connexin43 and connexin45 form gap junctions with different molecular permeabilities in osteoblastic cells. EMBO J. 13, 744-750 (1994)
27. Donahue, H.J., Li, Z., Zhou, Z. & Yellowley, C.E. Differentiation of human fetal osteoblastic cells and gap junctional intercellular communication. Am.J.Physiol.(Cell Physiol.) 278, C315-C322 (2000)
28. Gluhak-Heinrich, J., Gu, S., Pavlin, D. & Jiang, J.X. Mechanical loading stimulates expression of connexin 43 in aveolar bone cells in the tooth movement model. Cell Commun.Adhes. 13, 115-125 (2006)
29. Jeansonne, B.G., Feagin, F.F., Mcminn, R.W., Shoemarker, R.L. & Rehm, W.S. Cell-to cell communication of osteoblasts. J.Dent.Res, 58, 1415-1423 (1979)
30. Schirrmacher, K., Ramanan, S.V., Cronin, K., Peterson, E. & Brink, P.R. Voltage sensitivity of gap junction currents in rat osteoblast-like cells. Biochim.Biophys.Acta. 1327, 89-96 (1997)
31. Ushiyama, J. Gap junctions between odontoblasts revealed by transjuctional flux of fluorescent tracers. Cell Tissue Res. 258, 611-616 (1989)
32. Palumbo, C., Palazzini, S. & Marotti, G. Morphological study of intercellular junctions during osteocyte differentiation. Bone 11, 401-406 (1990)
33. Yamguchi, D.T., Ma, D., Lee, A., Huang, J. & Gruber, H.E. Isolation and characterization of gap junctions in the osteoblastic MC3T3-E1 cell line. J.Bone Miner.Res. 9, 791-803 (1994)
34. Doty, S.B. Morphological evidence of gap junctions between bone cells. Calcif.Tissue Int. 33, 509-512 (1981)
35. Jones, S.J., Gray, C., Sakamaki, H., Arora, M., Boyde, A., Gourdie, R. & Green, C. The incidence and size of gap junctions between the bone cells in rat calvaria. Anat.Embryol. 187, L343-352 (1993)
36. Shapiro, F. Variable conformation of gap junctions linking bone cells: a transmission electron microscopic study of linear, stacked linear, curvilinear, oval and annular junctions. Calcif.Tissue Int. 61, 285-293 (1997)
37. Stains, J.P. & Civitelli, R. Gap junctions in skeletal development and function. Biiochim.Biophys.Acta. 1719, 69-81 (2005)
38. Paznekas, W.A., Boyadjiev, S.A., Shapiro, R.E., Daniels, O., Wollnik, B., Keegan, C.E., Innis, J.W., Dinulos, M.B., Christian, C., Hannibal, M.C. & Jabs, E.W. Connexin 43 (GJA1) mutations cause the pleiotropic phenotypes of oculodentodigital dysplasia. Am.J.Hum.Genet. 72, 408-418 (2003)
39. Kjaer, K.W., Hansen, L., Eiberg, H., Leicht, P., Opitz, J.M. & Tommerup, N. Novel connexin 43 (GJA1) mutation causes oculo-dento-digital dysplasia with curly hair. Am.J.Med. Gene. 127A, 152-157 (2004)
40. Richardson, R., Donnai, D., Meire, F. & Dixon, M.J. Expression of Gjal correlates with the phenotype observed in oculodentodigital syndrome/type III syndactyly. J.Med.Genet. 41, 60-67 (2004)
41. van Steensel, M., Spruijt, L., van der Burgt, I., Bladergroen, R.S., Vermeer, M., Steijlen, P.M. & van Geel, M. A 2-bp deletion in the GJA1 gene is associated with oculo-dento-digital dysplasia with palmoplantar keratoderma. Am.J.Med.Genet. 132, 171-174 (2005)
42. Lai, A., Le, D.N., Paznekas, W.A., Gifford, W.D., Jabs, E.W. & Charles, A.C. Oculodentodigital dysplasia connexin43 mutations results in non-functional connexin hemichannels and gap junctions in C6 glioma cells. J.Cell Sc. 119, 532-541 (2006)
43. Lecanda, F., Warlow, P.M., Sheikh, S., Furlan, F., Steinberg, T.H. & Civitelli, R. Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction. J. Cell Biol. 151, 931-943 (2000)
44. Ya, J., Erdtsieck-Ernste, E.B., de Boer, P.A., van Kempen, M.J., Jongsma, H., Gros, D., Moorman, A.F. & Lamers, W.H. Heart defects in connexin43-deficient mice. Circ.Res. 82, 360-366 (1998)
45. Becker, D.L., McGonnell, I., Makarenkova, H.P., Patel, K., Tickle, C., Lorimer, J. & Green, C.R. Roles for al connexin in morphogenesis of chick embryos revealed using a novel antisense approach. Dev.Gene. 24, 33-42 (1999)
46. McGonnell, I.M, Green, C.R., Tickle, C. & Becker, D.L. Connexin43 gap junction protein plays an essential role in morphogenesis of the embryonic chick face. Dev.Dyn. 222, 420-438 (2001)
47. Law, L.Y., Lin, J.S., Becker, C.R. & Green, C.R. Knockdown of connexin43-mediated regulation of the zone of polarizing activity in the developing chick limb leads to digit truncation. Dev.Growth Differ. 44, 537-547 (2002)
48. Minkoff, R., Bales, E.S., Kerr, C.A. & Struss, W.E. Antisense oligonucleotide blockade of connexin expression during embryonic bone formation: evidence of functional compensation within a multigene family. Dev.Gene. 24, 43-56 (1999)
49. Castro C.H., Stains, J.P., Sheikh, S., Szejnfeld, V.L., Willecke, K., Theis, M. & Civitelli, R. Development of mice with osteoblast-specific connexin43 gene deletion. Cell Commun.Adhes. 10, 445-450 (2003)
50. Iovine, M.K., Higgins, E.P., Hindes, A., Coblitz, B. & Johnson, S.L. Mutations in connexin43 (GJA1) perturb bone growth in zebrafish fins. Dev.Biol. 278, 208-219 (2005)
51. Villars, F., Guillotin, B., Amédée, T., Dutoya, S., Bordenave, L., Bareille, R. & Amédée, J. Effect of HUVEC on human osteoprogenitor cell differentiation needs heterotypic gap junction communication. Am.J.Phsiol. 282, C775-C785 (2002)
52. Lecanda, F., Towler, D.A., Ziambaras, K., Cheng, S.-L., Koval, M., Steinberg, T.H. & Civitelli, R. Gap junctional communication modulates gene expression in osteoblastic cells. Mole.Biol.Cell 9, 2249-2258 (1998)
53. Li, Z., Zhou, Z., Yellowley, C.E. & Donahue, H.J. Inhibiting gap junctional intercellular communication alters expression of differentiation markers in osteoblastic cells. Bone 25, 661-666 (1999)
54. Schiller, P.C., D'Ippolito, G., Balkan, W., Roos, B.A. & Howard, G.A. Gap-junctional communication is required for the maturation process of osteoblastic cells in culture. Bone 28, 362-369 (2001)
55. Upham, B.L., Suzuki, J., Chen, G., Wang, Y., McCabe, L.R., Chang, C.-C., Krutovskikh, V.A., Yamasaki, H. & Trosko, I.E. Reduced gap junctional intercellular communication and altered biological effects in mouse osteoblast and rat liver oval cell lines transfected with dominant-negative connexin 43. Mol.Carcinog. 37, 192-201 (2003)
56. Schiller, P.C., D'Ippolito, G., Brambilla, R., Roos, B.A. & Howard, G.A. Inhibition of gap-junctional communication induces the trans- differentiation of osteoblasts to an adipocytic phenotype in vitro. J.Biol.Chem. 276, 14133-14138 (2001)
57. Gramsch, B., Gabriel, H.D., Wiemann, M., Grummer, R., Winterhager, E., Bingmann, D. & Schirrmacher, K. Enhancement of connexin 43 expression increases proliferation and differentiation of an osteoblast-like cell line. Exp.Cell Res. 264, 397-407 (2001)
58. Schiller, P.C., D'Ippolito, G., Balkan, W., Roos, B.A. & Howard, G.A. Gap-junctional communication mediates parathyroid hormone stimulation of mineralization in osteoblastic cultures. Bone 28, 38-44 (2001)
59. Van der Molen, M.A., Rubin, C.T., Mcleod, K.J., Mccauley, L.K. & Donahue, H.J. Gap junctional intercellular communication contributes to hormonal responsiveness in osteoblastic networks. J.Biol.Chem. 271, 12165-12171 (1996)
60. Guillotin, B., Bourget, C., Remy-Zolgadri, M., Bareille, R., Fernandez, P., Conrad, V. & Amedee-Vilamitjana, J. Human primary endothelial cells stimulate human osteoprogenitor cell differentiation. Cell Physiol.Biochem. 14, 325-332 (2004)
61. Koval, M., Geist, S.T., Westphale, E.M., Kemendy, A.E., Civitelli, R., Beyer, B.C. & Steinberg, T.H. Transfected connexin45 alters gap junction permeability in cells expressed endogenous connexin43. J.Cell Biol. 130, 987-1005 (1995)
62. Laing, J.G., Manley-Markowski, R.N., Koval, M., Civitelli, R. & Steinberg, T.H. Connexin45 interacts with zonula occludens-1 and connexin43 in osteoblastic cells. J.Biol.Chem. 276, 23051-23055 (2001)
63. Stains, J.P. & Civitelli, R. Gap junctions regulate extracellular signal-regulated kinase (ERK) signaling to affect gene transcription. Mol.Biol.Cell 16, 64-72 (2005)
64. Chen, J.R., Chatterjee, B., Meyer, R., Yu, J.C., Borke, J.L., Isales, C.M., Kirby, ML., Lo, C.W. & Bollag, R.J. Tbx2 represses expression of connexin43 in osteoblastic-like cells. Calcif. Tissue Int. (2004)
65. Pizard, A., Burgon, P.O., Paul, D.L., Bruneau, B.G., Seidman, C.E. & Seidman, J.G. Connexin 40, a target of transcription factor Tbx5, patterns wrist, digits, and sternum. Mol.Cell Biol. 25, 5073-5083 (2005)
66. Ilvesaro, J., Vããnãnen, K. & Tuukkanen, J. Bone-resorbing osteoclasts contain gap junctional connexin-43. J.Bone Miner.Res. 15, 919-926 (2000)
67. Ilvesaro J. & Tuukkanen, J. Gap-junctional regulation of osteoclast function. Crit.Rev.Eukaryot.Gene Expr. 13, 133-146 (2003)
68. Ransjo, M., Sahli, J. & Lie, A. Expression of connexin43 mRNA in microisolated murine osteoclasts and regulation of bone resorption in vitro by gap junction inhibitors. Biochem.Biophys.Res.Commun. 303, 1179-1185 (2003)
69. Ilvesaro, J., Tavi, P. & Tuukkanen, J. Connexinmimetic peptide Gap 27 decreases osteoclastic activity. BMC Musculoskelet.Disord 2, 10 (2001)
70. Matemba, S.F., Lie, A. & Ransjo, M. Regulation of osteoclastogenesis by gap junction communication. J.Cell Biochem. in press, (2006)
71. Civitelli, R., Ziambaras, K., Warlow, P.M., Lecanda, F., Nelson, T., Harley, J., Atal, N., Beyer, E.C. & Steinberg, T.H. Regulation of connexin43 expression and function by prostaglandin E2 (PGE2) and parathyroid hormone (PTH) in osteoblastic cells. J.Cell.Biochem. 68, 8-21 (1998)
72. Massas, R. & Benayahu, D. Parathyroid hormone effect on cell-to-cell communication in stromal and osteoblastic cells. J.Cell.Biochem. 69, 81-86 (1998)
73. Schiller, P.C., Mehta, P.P., Roos, B.A. & Howard, G.A. Hormonal regulation of intercellular communication: parathyroid hormone increases connexin 43 gene expression and gap-junctional communication in osteoblastic cells. Molecular Endocrinology 6, 1433-1440 (1992)
74. Schiller, P.C., Roos, B.A. & Howard, G.A. Parathyroid hormone up-regulation of connexin 43 gene expression in osteoblasts depends on cell phenotype. J.Bone Miner.Res. 12, 2005-2013 (1997)
75. Shen, V., Rifas, L., Kohler, G. & Peck, W.A. Prostaglandins change cell shape and increase intercellular gap junctions in osteoblasts cultured from rat fetal calvaria. J.Bone Miner.Res. 1, 243-249 (1986)
76. 2 is essential for gap junction-mediated intercellular communication between osteocyte-like MLO-Y4 cells in response to mechanical strain. Endocrinology 142, 3464-3473 (2001)
77. 2 receptor. J.Biol.Chem 278, 43146-43156 (2003)
78. Donahue, H.J., Mcleod, K.J., Rubin, C.T., Andersen, J., Grine, E.A., Hertzberg, E.L. & Brink, P.R. Cell-to-cell communication in osteoblastic networks: cell-line-dependent hormonal regulation of gap junction function. J.Bone Miner.Res. 10, 881-889 (1995)
79. Jorgensen, N.R., Teilmann, S.C., Henriksen, Z., Meier, E., Hansen, S.S., Jensen, J.E., Sorensen, O.H. & Petersen, J.S. The antiarrhythmic peptide analog rotigaptide (ZP123) stimulates gap junction intercellular communication in human osteoblasts and prevents decrease in femoral trabecular bone strength in ovariectomized rats. Endocrinology 146, 4745-4754 (2005)
80. Massas, R., Korenstein, R. & Benayahu, D. Estrogen modulation of osteoblastic cell-to-cell communication. J.Cell.Biochem. 69, 282-290 (1998)
81. Schirrmacher, K., Nonhoff, D., Wiemann, M., Peterson-Grine, E., Brink, P.R. & Bingmann, D. Effects of calcium on gap junctions between osteoblast-like cells in culture. Calcif.Tissue Int. 59, 259-264 (1996)
82. Rudkin, G.H., Yamaguchi, D.T., Ishida, K., Peterson, W.J., Bahadosingh, F., Thye, D. & Miller, T.A. Transforming growth factor-beta, osteogenin, and bone morphogenetic protein-2 inhibit intercellular communication and alter cell proliferation in MC3T3-E1 cells. J. Cell Physiol. 168, 433-441 (1996)
83. Kreiger, N.S., Sessler, N.B. & Bushinsky, D.A. Acidosis inhibits osteoblastic and stimulates osteoblastic activity. Am.J.Physiol. 262, F442-F448 (1992)
84. Yamaguchi, D.T., Huang, J.T. & Ma, D.F. Regulation of gap junction intercellular communication by ph in MC3T3-E1 osteoblastic cells. J.Bone Min.Res. 10, 1891-1899 (1995)
85. Yamaguchi, D.T. & Mia, D. Mechanism of pH regulation of connexin 43 expression in MC3T3-E1 cells. Biochem.Biophy.Res.Comm. 304, 736-739 (2003)
86. Romanello, M., Moro, L., Pirulli, D., Crovella, S. & D'Andrea, P. Effects of cAMP on intercellular coupling and osteoblast differentiation. Biochem.Biophy.Res.Commun. 282, 1138-1144 (2001)
87. Alford, A.I., Jacobs, C.R. & Donahue, H.J. Osillating fluid flow regulates gap junction communication in osteocytic MLO-Y4 cells by an ERK1/2 MAP kinase-dependent mechanism. Bone 33, 64-70 (2003)
88. Lacouture, M.E., Schaffer, J.L. & Klickstein, L.B. A comparison of type I collagen, fibronectin, and vitronectin in supporting adhesion of mechanically strained osteoblasts. J.Bone Miner.Res. 17, 481-492 (2002)
89. Nagahata, M., Tsuchiya, T., Ishiguro, T., Matsuda, N., Nakatsuchi, Y., Teramoto, A., Hachimori, A. & Abe, K. A novel function of N-cadherin and connexin43: marked enhancement of alkaline phosphatase activity in rat calvarial osteoblast exposed to sulfated hyaluronan. Biochem.Biophy.Res.Comm. 315, 603-611 (2004)
90. Nakaoka, R., Ahmed, S. & Tsuchiya, T. Hydroxy apaptite mirospheres enhance gap junctional intercellular communication of human osteoblasts composed of connexin 43 and 45. J.Biomed.Mater.Res. 74, 181-186 (2005)
91. Choudhary, S., Wadhwa, S., Raisz, L.G., Alander, C. & Pilbeam, C.C. Extracellular calcium is a potent inducer of cyclo-oxygenase-2 in murine osteoblasts through an ERK signaling pathway. J.Bone Miner.Res. 18, 1813-1824 (2003)
92. McIntire, S.L., Reimer, R.J., Schuske, K., Edwards, R.H. & Jorgensen, E.M. Identification and characterization of the vesicular GABA transporter. Nature 389, 870-876 (1997)
93. Jorgensen, N.R., Teilmann, S.C., Henriksen, Z., Civitelli, R., Sorensen, O.H. & Steinberg, T.H. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells. J.Biol.Chem. 278, 4082-4086 (2003)
94. D'Andrea, P. & Vittur, F. Gap junctions mediate intercellular calcium signalling in cultured articular chondrocytes. Cell Calcium 389-397 (1996)
95. D'Andrea, P., Calabrese, A., Capozzi, I., Grandolfo, M., Tonon, R. & Vittur, F. Intercellular Ca2+ wave in mechanically stimulated articular chondrocytes. Biorheology 37, 75-83 (2000)
96. D'Andrea, P., Calabrese, A. & Grandolfo, M. Intercellular calcium signaling between chondrocytes and snovial cells in co-culture. Biochem.J. 329, 681-687 (1998)
97. Grandolfo, M., Calabrese, A. & D'Andrea P. Mechanism of mechanically induced intercellular calcium waves in rabbit articular chondrocytes and in HIG-82 synovial cells. J.Bone Miner.Res. 13, 443-453 (1998)
98. Henriksen, Z., Hiken, J.F., Steinberg, T.H. & Jorgensen, N.R. The predominant mechanism of intercellular calcium wave propagation changes during long-term culture of human osteoblast-like cells. Cell Calcium 39, 435-444 (2006)
99. Goodenough, D.A. & Paul, D.L. Beyond the gap: Functions of unpaired connexon channels. Nature Rev. 4, 1-10 (2003)
100. Bennett, M.V.L., Contreras, J.E., Bukauskas, F.F. & Saez, J.C. New roles for astrocytes: Gap junction hemichannels have something to communicate. Trends Neurosci. 26, 610-617 (2003)
101. Ebihara, L. New roles for connexons. News Physiol.Sci. 18, 100-103 (2003)
102. Thimm, J., Mechler, A., Lin, H., Rhee, S. & Lal, R. Calcium-dependent open/chosed conformations and interfacial energy maps of reconstituted hemichannels. J.Biol.Chem. 280, 10646-10654 (2005)
103. Stout, C.E., Costantin, J.L., Naus, C.C.G. & Charles, A.C. Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J.Biol.Chem. 277, 10482-10488 (2002)
104. Vanoye, C.G., Vergara, L.A. & Reuss, L. Isolated epithelial cells from amphibian urinary bladder express functional gap junction hemichannels. Am.J.Phsiol.(Cell Physiol.) 276, C279-C284 (1999)
105. Gomes, P., Srinivas, S.P., Van Driessche, W., Vereecke, J. & Himpens, B. ATP release through connexin hemichannels in corneal endothelial cells. lnvest.Ophthalmol.Vis.Sci. 46, 1208-1218 (2005)
106. Zhang, D.-Q. & McMahon, D.G. Gating of retinal horizontal cell hemi gap junction channels by voltage, Ca2+, and retinoic acid. Mol.Vis. 7, 247-252 (2001)
107. Jorgensen, N.R., Henriksen, Z., Sørensen, O.H., Eriksen, E.F., Civitelli, R. & Steinberg, T.H. Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors. J.Biol.Chem. 277, 7574-7580 (2002)
108. Guyot, A. & Hanrahan, J.W. ATP release from human airway epithelial cells studied using a capillary cell culture system. J.Physiol. 545, 199-206 (2002)
109. Romanello, M. & D'Andrea, P. Dual mechanism of intercellular communication in HOBIT osteoblastic cells: A role for gap-junctional hemichannels. J.Bone Miner.Res. 16, 1465-1476 (2001)
110. + fluxes in intact cells. FASEB J. 15, 10-12 (2000)
111. Kamermans, M., Fahrenfort, I., Schultz, K., Janssen-Bienhold, U., Sjoerdsma, T. & Weiler, R. Hemichannelmediated inhibition in the outer retina. Science 292, 1178-1180 (2001)
112. Ye, Z.C., Wyeh, M.S., Baltao-Tekkok, S. & Ransom, B.R. Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J.Neurosci. 23, 3588-3596 (2003)
113. Hofer, A. & Dermietzel, R. Visualization and functional blocking of gap junction hemichannel (connexons) with antibodies against external loop domains in astrocytes. Glia 24, 141-154 (1998)
114. Boucher, S. & Bennett, S.A.L. Differential connexin expression, gap junction intercellular coupling, and hemichannel formation in NT2/D1 human neural progenitors and terminally differentiated hNT neurons. J.Neuro.Res 72, 393-404 (2003)
115. Contreras, J.E., Saez, J.C., Bukauskas, F.F. & Bennett, M.V.L. Gating and regulation of connexin 43 (Cx43) hemichannels. Proc.Nat.Acad.Sci.(USA) 100, 11388-11393 (2003)
116. Saez, J.C., Contreras, J.E., Bukauskas, F.F., Retamal, M.A. & Bennett, M.V.L. Gap junction hemichannels in astrocytes of the CNS. Acta Physiol.Scand. 179, 9-22 (2003)
117. John, S., Cesario, D. & Weiss, J.N. Gap junctional hemichannels in the heart. Acta Physiol.Scand. 179, 23-31 (2003)
118. Gomez-Hernandez, J.M., de Miguel, M., Larrosa, B., Gonzalez, D. & Barrio, L.C. Molecular basis of calcium regulation in connexin-32 hemichannels. Proc.Nat.Acad.Sci.(USA) 100, 16030-16035 (2003)
119. Jedamzik, B., Marten, I., Negezahayo, A., Ernst, A. & Kolb, H.A. Regulation of lens rCx46-formed hemichannels by activation of protein kinase C, external Ca(2+) and protons. J.Membrane Biol. 173, 39-46 (2000)
120. Valiunas, V. Biophysical properties of connexin-45 gap junction hemichannels studied in vertebrate cells. J.Gen.Physiol. 119, 147-164 (2002)
121. Quist, A.P., Rhee, S.K., Lin, H. & Lal, R. Physiological role of gap-junctional hemichannels: extracellular calcium-dependent isomotic volume regulation. J. Cell Biol. 148, 1063-1074 (2000)
122. Kondo, R.P., Wang, S.-Y., John, S.A., Weiss, J.N. & Goldhaber, J.I. Metabolic inhibition activates a non-selective current through connexin hemichannels in isolated ventricular myocytes. J.Mol.Cell Cardiol. 32, 1859-1872 (2000)
123. Contreras, J.E., Sánchez, H.A., Eugenin, E.A., Speidel, D., Theis, M., Willecke, K., Bukauskas, F.F., Bennett, M.V.L. & Sáez, J.C. Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Porc.Natl.Acad.Sci. 99, 495-500 (2002)
124. Plotkin, L.I. & Bellido, T. Bisphophonate-induced, hemichannel-mediated anti-apoptosis through the Src/ERK pathway: a gap junction-independent action of connexin43. Cell Commun.Adhes. 2001, 377-382 (2001)
125. Plotkin, L.I., Manolagas, S.C. & Bellido, T. Transduction of cell survival signals by connexin-43 hemichannels. J.Biol.Chem. 277, 8648-8657 (2002)
126. Jiang, J.X. & Cherian, P.P. Hemichannels formed by connexin 43 play an important role in the release of prostaglandin E2 by osteocytes in response to mechanical strain. Cell Commun.Adhes. 10, 259-264 (2003)
127. Cherian, P.P., Siller-Jackson, A.J., Gu, S., Wang, X., Bonewald, L.F., Sprague, E. & Jiang, J.X. Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Mol.Biol.Cell 16, 3100-3106 (2005)
128. Frost, H.M. Perspectives: A proposal general model of the "mechanostat". Anat.Rec. 244, 139-147 (1996)
129. Oster, G. (1989) in Cell shape: determinants, regulation and regulatory role (Stein, W.D. & Bronner, F., eds.), Cell mobility and tissue morphogenesis, pp. 33-61, Academic Press, San Diego
130. Cowin, S.C., Moss-Salentijin, L. & Moss, M.L. Candidates for the mechanosensory system in bone. J.Biomed.Eng. 113, 191-197 (1991)
131. Aarden, E.M., Burger, E.H. & Nijweide, P.J. Function of osteocytes in bone. J.Cell.Biochem. 55, 287-299 (1994)
132. Burger, E.H. & Klein-nulend, J. Mechanotransduction in bone-role of the lacunocanalicular network. FASEB J. 13, S101-S112 (1999)
133. Seliger, W.G. Tissue fluid movement in compact bone. Anat.Record 166, 247-255 (1970)
134. Knothe-Tate, M.L. & Knothe, U.P.N. Experimental elucidation of mechanical loading-induced fluid flow and its potential role in bone metabolism and functional adaptation. Am.J.Med.Sci. 316, 189-195 (1998)
135. Knothe-Tate, M.I. & Knothe, U. An ex vivo model to study transport processes and fluid flow in loaded bone. J.Biomechanics 33, 247-254 (2000)
136. Owan, I., Burr, D., Turner, C.H., Qiu, J.T.Y., Onyia, J.E. & Duncan, R.L. Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain. Am.J.Physiol. 42, C810-C815 (1997)
137. Smalt, R., Mitchell, F.T., Howard, R.L. & Chambers, T. J. Induction of NO and prostaglandin E2 in osteoblasts by wall stress but not mechanical strain. Am.J.Physiol. 273, E751-E758 (1997)
138. Klein-nulend, J., Van Der Plas, A., Semeins, C.M., Ajubi, N.B., Frangos, J.A., Nijweide, P.J. & Burger, E.H. Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. 9, 441-445 (1995)
139. Reich, K.M., Gay, C.V. & Frangos, J.A. Fluid shear stress as a mediator of osteoblast cyclic adenosine monophosphate production. J.Cell.Physiol. 143, 100-104 (1990)
140. Jacobs, C.R., Yellowley, C.E., Davis, B.R., Zhou, Z., Cimbala, J.M. & Donahue, H.J. Differential effect of steady versus oscillating flow on bone cells. J.Biomech. 31, 969-976 (1998)
141. Weinbaum, S., Cowin, S.C. & Zeng, Y. A model for the excitation of osteocytes by mechanical loading induced bone fluid shear stresses, J.Biomed.Eng. 27, 339-360 (1993)
142. Turner, C.H. & Forwood, M.R. What role does the osteocyte network play in bone adaptation? Bone 16, 283-285 (1995)
143. Mullender, M.G. & Huiskes, R. Osteocytes and bone lining cells: which are the best candidates for mechanosensors in cancellous bone? Bone 20, 527-532 (1997)
144. Burger, E.H., Klein-nulend, J., Van Der Plas, A. & Nijweide, P.J. Function of osteocytes in bone - their role in mechanotransduction. J.Nutrition 125, 2020S-2023S (1995)
145. Knothe Tate, M.L. "Whither flows the fluid in bone?" An osteocyte's perspective. J.Biomech. 36, 1409-1424 (2003)
146. Wang, L., Fritton, S.P., Weinbaum, S. & Cowin, S.C. On bone adaptation due to venous stasis. J.Biomech. 36, 1439-1451 (2003)
147. Zhang, D., Cowin, S.C. & Weinbaum, S. Electrical signal transmission and gap junction regulation in a bone cell network: a cable model for an osteon. Annal.Biomed.Engin. 25, 357-374 (1997)
148. Whitfield, J.F. Primary cilium - is it an osteocyte's strain-sensing flowmeter? J.Cell Biochem. 89, 233-237 (2003)
149. Ajubi, N.B., Klein-nulend, J., Nijweide, P.J., Vrijheidlammers, T., Alblas, M.J. & Burger, E.H. Pulsating fluid flow increases prostaglandin production by cultured chicken osteocytes-a cytoskeleton-dependent process. Biochem.Biophy.Res.Comm. 225, 62-68 (1996)
150. Turner, C.H., Forwood, M.R. & Otter, M.W. Mechanotransduction in bone: do bone cells act as sensors of fluid flow? FASEB J. 8, 875-878 (1994)
151. Nerussi, J.R., Sautier, J.M., Nicolas, V. & Forest, N. How osteoblasts become osteocytes: a decreasing matrix forming process. J.Biol.Buccale. 19, 75-82 (1991)
152. Knothe Tate, M.L., Adamson, J.R., Tami, A.E. & Bauer, T.W. The osteocytes. Int.J.Biochem.Cell Biol. 36, 1-8 (2004)
153. Kato, Y., Windle, J.J., Koop, B.A., Mundy, G.R. & Bonewald, L.F. Establishment of an osteocyte-like cell line, MLO-Y4. J.Bone Miner.Res. 12, 2014-2023 (1997)
154. Gu, G., Nars, M., Hentunen, T.A., Metsikkõ & Vããnãnen, H.K. Isolated primary osteocytes express functional gap junctions in vitro. Cell Tissue Res. 323, 263-271 (2006)
155. Yellowley, C.E., Li, Z., Zhou, Z., Jacobs, C.R. & Donahue, H. J. Functional gap junctions between osteocytic and osteoblastic cells. J.Bone Miner.Res. 15, 209-217 (2000)
156. Rubin, J., Rubin, C. & Jacob, C.R. Molecular pathway mediating mechanical signaling in bone. Gene 367, 1-16 (2006)
157. Donahue, H.J. Gap junctional intercellular communication in bone: A cellular basis for the mechanostat point. Calcif.Tissue 62, 85-88 (1998)
158. Donahue, H.J. Gap junctions and biophysical regulation of bone cell differentiation. Bone 26, 417-422 (2000)
159. Ziambaras, K., Lecanda, F., Steinberg, T.H. & Civitelli, R. Cyclic stretch enhances gap junctional communication between osteoblastic cells. J.Bone Miner.Res. 13, 218-228 (1998)
160. Van der Molen, M.A., Donahue, H.J., Rubin, C.T. & Mcleod, K.J. Osteoblastic networks with deficient coupling: differential effects of magnetic and electric field exposure. Bone 27, 227-231 (2000)
161. Saunders, M.M., You, J., Trosko, J.E., Yamasaki, H., Li, Z., Donahue, H.J. & Jacobs, C.R. Gap junctions and fluid flow response in MC3T3-E1 cells. Am.J.Physiol.(Cell Physiol.) 281, C1917-C1925 (2001)
162. Saunders, M.M., You, J., Zhou, Z., Li, Z., Yellowley, C.E., Kunze, E.L., Jacobs, C.R. & Donahue, H.J. Fluid flow-induced prostaglandin E2 response of osteoblastic ROS 17/2.8 cells is gap junction-mediated and independent of cytosolic calcium. Bone 32, 350-356 (2003)
163. Tang, L.Y., Cullen, D.M., Yee, J.A., Jee, W.S.S. & Kimmel, D.B. Prostaglandin 12 increases the skeletal response to mechanical loading. J.Bone Miner.Res. 12, 276-282 (1997)
164. Baylink, T.M., Mohan, S., Fitzsimmons, R.J. & Baylink, D.J. Evaluation of signal transduction mechanisms for the mitogenic effects of prostaglandin E2 in normal human bone cells in vitro. J.Bone Min.Res. 11, 1413-1418 (1996)
165. 2 on fracture callus in rabbit. Acta.Orthop.Scand. 64, 59-63 (1993)
166. Jee, W.S.S., Ueno, K., Deng, Y.P. & Woodbury, D.M. The effects of prostaglandin E2 in growing rats: increased metaphyseal hard tissue and corticoendosteal bone formation. Calcif.TissueInt. 37, 148-156 (1985)
167. Reilly, G.C., Haut, T.R., Yellowley, C.E., Donahue, H.J. & Jacobs, C.R. Fluid flow induced PGE2 release by bone cells is reduced by glycocalyx degradation whereas calcium signals are not. Biorheology 40, 591-603 (2003)
168. Contreras J.E., Sanchez, H.A., Veliz, L.P., Bukauskas, F.F., Bennett, M.V. & Saez, J.C. Role of connexin-based gap junction channels and hemichannels in ischemia-induced cell death in nervous tissue. Brain Res.Brain Res.Rev. 2004, 290-303 (2004)
169. Vergara, L., Bao, X., Cooper, M., Bello-Reuss, E. & Reuss, L. Gap junctional hemichannels are activated by ATP depletion in human renal proximal tubule cells. J.Membrane Biol. 196, 173-184 (2003)
170. Vergara, L., Bao, X., Bello-Reuss, E. & Reuss, L. Do connexin 43 gap junctional hemichannels activate and cause cell damage during ATP depletion of renal-tubule cells? Acta Physiol. Scand. 179, 33-38 (2003)
171. Kim, D.Y., Kam, Y., Koo, S.K. & Joe, C.O. Gating connexin 43 channels reconstituted in lipid vesicles by mitogen-activated protein kinase phosphorylation. J.Biol.Chem. 274, 5581-5587 (1999)
172. Bao, X., Reuss, L. & Altenberg, G.A. Regulation of purified and reconstituted connexin 43 hemichannels by protein kinase C-mediated phosphorylation of serine 368. J.Biol.Chem. 279, 20058-20066 (2004)
173. Retamal, M.A., Cortes, C.J., Reuss, L., Bennett, M.V. & Sáez, J. S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: induction by oxidant stress and reversal by reducing agents. Proc.Nat.Acad.Sci.(USA) 103, 4475-4480 (2006)
174. Cherian, P.P., Siller-Jackson, A.J., Burra, S., Gu, S., Bonewald, L.F., Sprague, E. & Jiang, J.X. Potential role of alpha5 integrin as a mechanosensor in the opening of hemichannels for the release of prostaglandin in response to mechanical stress. J.Bone Min.Res. 20 (suppl. 1), S25 (2005)
175. Lampe, P.D., Nguyen, B.P., Gil, S., Usui, M., Olerud, J., Takada, Y. & Carter, W.G. Cellular interaction of integrin alpha3betal with laminin 5 promotes gap junction communication. J. Cell Biol. 143, 1735-1747 (1998)
176. Guo, Y., Martinez-Williams, C. & Rannels, E. Gap junction-microtubule associations in rat alveolar epithelial cells. Am J.Physiol.Lung Cell Mol.Physiol. 285, L1213-L1221 (2003)
177. Guo, Y., Martinez-Williams, C., Yellowley, C.E., Donahue, H.J. & Rannels, D.E. Connexin expression by alveolar epithelial cells is regulated by extracellular matrix. Am J.Physiol.Lung Cell Mol.Physiol. 280, L191-L202 (2001)
178. Rundus, V.R., Marshall, G.B., Parker, S.B., Bales, E.S., Hertzberg, E.L. & Minkoff, R. Association of cell and substrate adhesion molecules with connexin43 during intramemebranous bone formation. Histochem. J. 30, 879-896 (1998)
179. Wang, N. & Ingber, D.E. Control of cytoskeletal mechanisms by extracellular matrix, cell shape and mechanical tension. Science 66, 2181-2189 (1993)
180. Chen, C.S., Tan, J. & Tien, J. Mechanostransduction at cell-matrix and cell-cell contacts. Ann.Rev.Biomed.Eng. 6, 275-302 (2004)
181. Salter, D.M., Robb, J.E. & Wright, M.O. Electrophysiological responses of human bone cells to mechanical stimulation: evidence for specific integrin function in mechanotransduction. J.Bone Miner.Res. 12, 1133-1141 (1997)
182. Katsum, A., Orr, A.W., Tzima, E. & Schwartz, M.A. Integrin in mechanotransduction. J.Biol.Chem. 279, 12001-12004 (2004)
183. Hughes, D.E., Salter, D.M., Dedhar, S. & Simpson, R. Integrin expression in human bone. J.Bone Min.Res. 8, 527-533 (1993)
184. Bennett, J.H., Carter, D.H., Alavi, A.L., Beresford, J.N. & Walsh, S. Patterns of integrin expression in a human mandibular explant model of osteoblast differentiation. Arch.Oral Biol. 46, 229-238 (2001)
185. McCarthy, A.D., Uemura, T., Etcheverry, S.B. & Cortizo, A.M. Advance glycation endproducts interfere with integrin-mediated osteoblastic attachment to a type-1 collagen matrix. Int.J.Biochem.Cell Biol. 36, 840-848 (2004)
186. Ostergaard, K., Salter, D.M., Petersen, J., Bendtzen, K., Hvolris, J. & Andersen, C.B. Expression of I. and r and subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads. Am.Rheum.Dis. 57, 303-308 (1998)
187. Plotkin, L.I., Mathov, I., Aguirre, J.I., Parfitt, A.M., Manolagas, S.C. & Bellido, T. Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, src kinase and ERKs. Am.J.Physiol.(Cell Physiol.) 289, 633-643 (2005)