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Calcified Tissue International

Erschienen in:

01.01.2014 | Original Research

Molecular Mechanisms of Osteoblast/Osteocyte Regulation by Connexin43

verfasst von: Joseph P. Stains, Marcus P. Watkins, Susan K. Grimston, Carla Hebert, Roberto Civitelli

Erschienen in: Calcified Tissue International | Ausgabe 1/2014

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Abstract

Osteoblasts, osteocytes, and osteoprogenitor cells are interconnected into a functional network by gap junctions formed primarily by connexin43 (Cx43). Over the past two decades, it has become clear that Cx43 is important for the function of osteoblasts and osteocytes. This connexin contributes to the acquisition of peak bone mass and is a major modulator of cortical modeling. We review key data from human and mouse genetics on the skeletal consequences of ablation or mutation of the Cx43 gene (Gja1) and the molecular mechanisms by which Cx43 regulates the differentiation, function, and survival of osteogenic lineage cells. We also discuss putative second messengers that are communicated by Cx43 gap junctions, the role of hemichannels, and the function of Cx43 as a scaffold for signaling molecules. Current knowledge demonstrates that Cx43 is more than a passive channel; rather, it actively participates in the generation and modulation of cellular signals that drive skeletal development and homeostasis.

Segretain D, Falk MM (2004) Regulation of connexin biosynthesis, assembly, gap junction formation, and removal. Biochim Biophys Acta 1662:3–21PubMedCrossRef

Goodenough DA, Paul DL (2003) Beyond the gap: functions of unpaired connexon channels. Nat Rev Mol Cell Biol 4:285–294PubMedCrossRef

Civitelli R (2008) Cell–cell communication in the osteoblast/osteocyte lineage. Arch Biochem Biophys 473:188–192PubMedCentralPubMedCrossRef

Civitelli R, Stains JP, Shin CS, Jørgensen N (2008) Intercellular junctions and cell–cell communication in the skeletal system. In: Bilezikian JP, Raisz LG, Martin TJ (eds) Principles of bone biology. Academic Press, San Diego, pp 425–444CrossRef

Paic F, Igwe JC, Nori R, Kronenberg MS, Franceschetti T, Harrington P, Kuo L, Shin DG, Rowe DW, Harris SE, Kalajzic I (2009) Identification of differentially expressed genes between osteoblasts and osteocytes. Bone 45:682–692PubMedCentralPubMedCrossRef

Paznekas WA, Boyadjiev SA, Shapiro RE, Daniels O, Wollnik B, Keegan CE, Innis JW, Dinulos MB, Christian C, Hannibal MC, Jabs EW (2003) Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet 72:408–418PubMedCentralPubMedCrossRef

Paznekas WA, Karczeski B, Vermeer S, Lowry RB, Delatycki M, Laurence F, Koivisto PA, Van Maldergem L, Boyadjiev SA, Bodurtha JN, Jabs EW (2009) GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype. Hum Mutat 30:724–733PubMedCrossRef

Flenniken AM, Osborne LR, Anderson N, Ciliberti N, Fleming C, Gittens JE, Gong XQ, Kelsey LB, Lounsbury C, Moreno L, Nieman BJ, Peterson K, Qu D, Roscoe W, Shao Q, Tong D, Veitch GI, Voronina I, Vukobradovic I, Wood GA, Zhu Y, Zirngibl RA, Aubin JE, Bai D, Bruneau BG, Grynpas M, Henderson JE, Henkelman RM, McKerlie C, Sled JG, Stanford WL, Laird DW, Kidder GM, Adamson SL, Rossant J (2005) A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia. Development 132:4375–4386PubMedCrossRef

Gong XQ, Shao Q, Langlois S, Bai D, Laird DW (2007) Differential potency of dominant negative connexin43 mutants in oculodentodigital dysplasia. J Biol Chem 282:19190–19202PubMedCrossRef

10.

McLachlan E, Plante I, Shao Q, Tong D, Kidder GM, Bernier SM, Laird DW (2008) ODDD-linked Cx43 mutants reduce endogenous Cx43 expression and function in osteoblasts and inhibit late stage differentiation. J Bone Miner Res 23:928–938PubMedCrossRef

11.

Dobrowolski R, Sasse P, Schrickel JW, Watkins M, Kim JS, Rackauskas M, Troatz C, Ghanem A, Tiemann K, Degen J, Bukauskas FF, Civitelli R, Lewalter T, Fleischmann BK, Willecke K (2008) The conditional connexin43G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans. Hum Mol Genet 17:539–554PubMedCentralPubMedCrossRef

12.

Roscoe W, Veitch GI, Gong XQ, Pellegrino E, Bai D, McLachlan E, Shao Q, Kidder GM, Laird DW (2005) Oculodentodigital dysplasia-causing connexin43 mutants are non-functional and exhibit dominant effects on wild-type connexin43. J Biol Chem 280:11458–11466PubMedCrossRef

13.

Watkins M, Grimston SK, Norris JY, Guillotin B, Shaw A, Beniash E, Civitelli R (2011) Osteoblast connexin43 modulates skeletal architecture by regulating both arms of bone remodeling. Mol Biol Cell 22:1240–1251PubMedCentralPubMedCrossRef

14.

Becker DL, McGonnell I, Makarenkova HP, Patel K, Tickle C, Lorimer J, Green CR (1999) Roles for alpha 1 connexin in morphogenesis of chick embryos revealed using a novel antisense approach. Dev Genet 24:33–42PubMedCrossRef

15.

Lecanda F, Warlow PM, Sheikh S, Furlan F, Steinberg TH, Civitelli R (2000) Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction. J Cell Biol 151:931–944PubMedCrossRef

16.

Reaume AG, de Sousa PA, Kulkarni S, Langille BL, Zhu D, Davies TC, Juneja SC, Kidder GM, Rossant J (1995) Cardiac malformation in neonatal mice lacking connexin43. Science 267:1831–1834PubMedCrossRef

17.

Rodda SJ, McMahon AP (2006) Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133:3231–3244PubMedCrossRef

18.

Chung DJ, Castro CH, Watkins M, Stains JP, Chung MY, Szejnfeld VL, Willecke K, Theis M, Civitelli R (2006) Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43. J Cell Sci 119:4187–4198PubMedCrossRef

19.

Grimston SK, Brodt MD, Silva MJ, Civitelli R (2008) Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the connexin43 gene (Gja1). J Bone Miner Res 23:879–886PubMedCrossRef

20.

Gonzalez-Nieto D, Li L, Kohler A, Ghiaur G, Ishikawa E, Sengupta A, Madhu M, Arnett JL, Santho RA, Dunn SK, Fishman GI, Gutstein DE, Civitelli R, Barrio LC, Gunzer M, Cancelas JA (2012) Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors. Blood 119:5144–5154PubMedCrossRef

21.

Schajnovitz A, Itkin T, D’Uva G, Kalinkovich A, Golan K, Ludin A, Cohen D, Shulman Z, Avigdor A, Nagler A, Kollet O, Seger R, Lapidot T (2011) CXCL12 secretion by bone marrow stromal cells is dependent on cell contact and mediated by connexin-43 and connexin-45 gap junctions. Nat Immunol 12:391–398PubMedCrossRef

22.

Zhang Y, Paul EM, Sathyendra V, Davison A, Sharkey N, Bronson S, Srinivasan S, Gross TS, Donahue HJ (2011) Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS ONE 6:e23516PubMedCentralPubMedCrossRef

23.

Bivi N, Condon KW, Allen MR, Farlow N, Passeri G, Brun LR, Rhee Y, Bellido T, Plotkin LI (2012) Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. J Bone Miner Res 27:374–389PubMedCentralPubMedCrossRef

24.

Bivi N, Nelson MT, Faillace ME, Li J, Miller LM, Plotkin LI (2012) Deletion of Cx43 from osteocytes results in defective bone material properties but does not decrease extrinsic strength in cortical bone. Calcif Tissue Int 91:215–224PubMedCentralPubMedCrossRef

25.

Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien CA (2011) Matrix-embedded cells control osteoclast formation. Nat Med 17:1235–1241PubMedCentralPubMedCrossRef

26.

Kalajzic I, Matthews BG, Torreggiani E, Harris MA, Pajevic PD, Harris SE (2012) In vitro and in vivo approaches to study osteocyte biology. Bone 54:296–306PubMedCrossRef

27.

Plotkin LI, Bellido T (2013) Beyond gap junctions: connexin43 and bone cell signaling. Bone 52:157–166PubMedCentralPubMedCrossRef

28.

Grimston SK, Watkins MP, Brodt MD, Silva MJ, Civitelli R (2012) Enhanced periosteal and endocortical responses to axial tibial compression loading in conditional connexin43 deficient mice. PLoS ONE 7:e44222PubMedCentralPubMedCrossRef

29.

Grimston SK, Goldberg DB, Watkins M, Brodt MD, Silva MJ, Civitelli R (2011) Connexin43 deficiency reduces the sensitivity of cortical bone to the effects of muscle paralysis. J Bone Miner Res 26:2151–2160PubMedCentralPubMedCrossRef

30.

Grimston SK, Silva MJ, Civitelli R (2007) Bone loss after temporarily induced muscle paralysis by Botox is not fully recovered after 12 weeks. Ann N Y Acad Sci 1116:444–460PubMedCrossRef

31.

Grimston SK, Screen J, Haskell JH, Chung DJ, Brodt MD, Silva MJ, Civitelli R (2006) Role of connexin43 in osteoblast response to physical load. Ann N Y Acad Sci 1068:214–224PubMedCrossRef

32.

Lloyd SA, Lewis GS, Zhang Y, Paul EM, Donahue HJ (2012) Connexin 43 deficiency attenuates loss of trabecular bone and prevents suppression of cortical bone formation during unloading. J Bone Miner Res 27:2359–2372PubMedCentralPubMedCrossRef

33.

Lecanda F, Towler DA, Ziambaras K, Cheng SL, Koval M, Steinberg TH, Civitelli R (1998) Gap junctional communication modulates gene expression in osteoblastic cells. Mol Biol Cell 9:2249–2258PubMedCentralPubMedCrossRef

34.

Li Z, Zhou Z, Saunders MM, Donahue HJ (2006) Modulation of connexin43 alters expression of osteoblastic differentiation markers. Am J Physiol Cell Physiol 290:C1248–C1255PubMedCrossRef

35.

Li Z, Zhou Z, Yellowley CE, Donahue HJ (1999) Inhibiting gap junctional intercellular communication alters expression of differentiation markers in osteoblastic cells. Bone 25:661–666PubMedCrossRef

36.

Donahue HJ, Li Z, Zhou Z, Yellowley CE (2000) Differentiation of human fetal osteoblastic cells and gap junctional intercellular communication. Am J Physiol Cell Physiol 278:C315–C322PubMed

37.

Schiller PC, D’Ippolito G, Balkan W, Roos BA, Howard GA (2001) Gap-junctional communication is required for the maturation process of osteoblastic cells in culture. Bone 28:362–369PubMedCrossRef

38.

Schiller PC, D’Ippolito G, Balkan W, Roos BA, Howard GA (2001) Gap-junctional communication mediates parathyroid hormone stimulation of mineralization in osteoblastic cultures. Bone 28:38–44PubMedCrossRef

39.

Lima F, Niger C, Hebert C, Stains JP (2009) Connexin43 potentiates osteoblast responsiveness to fibroblast growth factor 2 via a protein kinase C-delta/Runx2-dependent mechanism. Mol Biol Cell 20:2697–2708PubMedCentralPubMedCrossRef

40.

Niger C, Buo AM, Hebert C, Duggan BT, Williams MS, Stains JP (2012) ERK acts in parallel to PKCdelta to mediate the connexin43-dependent potentiation of Runx2 activity by FGF2 in MC3T3 osteoblasts. Am J Physiol Cell Physiol 302:C1035–C1044PubMedCrossRef

41.

Xiao G, Jiang D, Gopalakrishnan R, Franceschi RT (2002) Fibroblast growth factor 2 induction of the osteocalcin gene requires MAPK activity and phosphorylation of the osteoblast transcription factor, Cbfa1/Runx2. J Biol Chem 277:36181–36187PubMedCrossRef

42.

Kim HJ, Kim JH, Bae SC, Choi JY, Kim HJ, Ryoo HM (2003) The protein kinase C pathway plays a central role in the fibroblast growth factor-stimulated expression and transactivation activity of Runx2. J Biol Chem 278:319–326PubMedCrossRef

43.

Park OJ, Kim HJ, Woo KM, Baek JH, Ryoo HM (2010) FGF2-activated ERK mitogen-activated protein kinase enhances Runx2 acetylation and stabilization. J Biol Chem 285:3568–3574PubMedCrossRef

44.

Stains JP, Lecanda F, Screen J, Towler DA, Civitelli R (2003) Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters. J Biol Chem 278:24377–24387PubMedCrossRef

45.

Stains JP, Civitelli R (2005) Gap junctions regulate extracellular signal-regulated kinase signaling to affect gene transcription. Mol Biol Cell 16:64–72PubMedCentralPubMedCrossRef

46.

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29PubMedCrossRef

47.

Niger C, Lima F, Yoo DJ, Gupta RR, Buo AM, Hebert C, Stains JP (2011) The transcriptional activity of osterix requires the recruitment of Sp1 to the osteocalcin proximal promoter. Bone 49:683–692PubMedCentralPubMedCrossRef

48.

Hoptak-Solga AD, Nielsen S, Jain I, Thummel R, Hyde DR, Iovine MK (2008) Connexin43 (GJA1) is required in the population of dividing cells during fin regeneration. Dev Biol 317:541–548PubMedCentralPubMedCrossRef

49.

Iovine MK, Higgins EP, Hindes A, Coblitz B, Johnson SL (2005) Mutations in connexin43 (GJA1) perturb bone growth in zebrafish fins. Dev Biol 278:208–219PubMedCrossRef

50.

Sims K Jr, Eble DM, Iovine MK (2009) Connexin43 regulates joint location in zebrafish fins. Dev Biol 327:410–418PubMedCentralPubMedCrossRef

51.

Ton QV, Iovine MK (2012) Semaphorin3d mediates Cx43-dependent phenotypes during fin regeneration. Dev Biol 366:195–203PubMedCentralPubMedCrossRef

52.

Ton QV, Iovine MK (2013) Determining how defects in connexin43 cause skeletal disease. Genesis 51:75–82PubMedCrossRef

53.

Jilka RL, Noble B, Weinstein RS (2013) Osteocyte apoptosis. Bone 54:264–271PubMedCrossRef

54.

Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K (2007) Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab 5:464–475PubMedCrossRef

55.

Bivi N, Lezcano V, Romanello M, Bellido T, Plotkin LI (2011) Connexin43 interacts with betaarrestin: a pre-requisite for osteoblast survival induced by parathyroid hormone. J Cell Biochem 112:2920–2930PubMedCentralPubMedCrossRef

56.

Cherian PP, Siller-Jackson AJ, Gu S, Wang X, Bonewald LF, Sprague E, Jiang JX (2005) Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Mol Biol Cell 16:3100–3106PubMedCentralPubMedCrossRef

57.

Siller-Jackson AJ, Burra S, Gu S, Xia X, Bonewald LF, Sprague E, Jiang JX (2008) Adaptation of connexin 43-hemichannel prostaglandin release to mechanical loading. J Biol Chem 283:26374–26382PubMedCrossRef

58.

Genetos DC, Kephart CJ, Zhang Y, Yellowley CE, Donahue HJ (2007) Oscillating fluid flow activation of gap junction hemichannels induces ATP release from MLO-Y4 osteocytes. J Cell Physiol 212:207–214PubMedCentralPubMedCrossRef

59.

Batra N, Burra S, Siller-Jackson AJ, Gu S, Xia X, Weber GF, DeSimone D, Bonewald LF, Lafer EM, Sprague E, Schwartz MA, Jiang JX (2012) Mechanical stress-activated integrin alpha₅beta₁ induces opening of connexin 43 hemichannels. Proc Natl Acad Sci USA 109:3359–3364PubMedCrossRef

60.

Taylor AF, Saunders MM, Shingle DL, Cimbala JM, Zhou Z, Donahue HJ (2007) Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions. Am J Physiol Cell Physiol 292:C545–C552PubMedCrossRef

61.

Jiang J, Burra S, Harris S, Zhao H, Johnson M, Bonewald LF (2010) Inhibiting gap junction function in osteocytes, but not Cx43 hemichannel function results in defects in skeletal structure and bone mass. J Bone Miner Res. http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=b7a23bf22-371f-4146-4149eac-4190e4148ceee3856

62.

Thi MM, Islam S, Suadicani SO, Spray DC (2012) Connexin43 and pannexin1 channels in osteoblasts: who is the “hemichannel”? J Membr Biol 245:401–409PubMedCentralPubMedCrossRef

63.

Sosinsky GE, Boassa D, Dermietzel R, Duffy HS, Laird DW, MacVicar B, Naus CC, Penuela S, Scemes E, Spray DC, Thompson RJ, Zhao HB, Dahl G (2011) Pannexin channels are not gap junction hemichannels. Channels (Austin) 5:193–197CrossRef

64.

D’Hondt C, Ponsaerts R, De Smedt H, Vinken M, De Vuyst E, De Bock M, Wang N, Rogiers V, Leybaert L, Himpens B, Bultynck G (2011) Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum. Cell Signal 23:305–316PubMedCrossRef

65.

D’Hondt C, Ponsaerts R, De Smedt H, Bultynck G, Himpens B (2009) Pannexins, distant relatives of the connexin family with specific cellular functions? BioEssays 31:953–974PubMedCrossRef

66.

Bond SR, Lau A, Penuela S, Sampaio AV, Underhill TM, Laird DW, Naus CC (2011) Pannexin 3 is a novel target for Runx2, expressed by osteoblasts and mature growth plate chondrocytes. J Bone Miner Res 26:2911–2922PubMedCrossRef

67.

Ishikawa M, Iwamoto T, Nakamura T, Doyle A, Fukumoto S, Yamada Y (2011) Pannexin 3 functions as an ER Ca²⁺ channel, hemichannel, and gap junction to promote osteoblast differentiation. J Cell Biol 193:1257–1274PubMedCrossRef

68.

Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T (2005) Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 280:7317–7325PubMedCrossRef

69.

Plotkin LI, Manolagas SC, Bellido T (2002) Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem 277:8648–8657PubMedCrossRef

70.

Rogers MJ, Frith JC, Luckman SP, Coxon FP, Benford HL, Monkkonen J, Auriola S, Chilton KM, Russell RG (1999) Molecular mechanisms of action of bisphosphonates. Bone 24:73S–79SPubMedCrossRef

71.

Bellido T, Plotkin LI (2011) Novel actions of bisphosphonates in bone: preservation of osteoblast and osteocyte viability. Bone 49:50–55PubMedCentralPubMedCrossRef

72.

Plotkin LI, Lezcano V, Thostenson J, Weinstein RS, Manolagas SC, Bellido T (2008) Connexin 43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts in vivo. J Bone Miner Res 23:1712–1721PubMedCrossRef

73.

Watkins MP, Norris JY, Grimston SK, Zhang X, Phipps RJ, Ebetino FH, Civitelli R (2012) Bisphosphonates improve trabecular bone mass and normalize cortical thickness in ovariectomized, osteoblast connexin43 deficient mice. Bone 51:787–794PubMedCentralPubMedCrossRef

74.

Idris AI, Rojas J, Greig IR, Van’t Hof RJ, Ralston SH (2008) Aminobisphosphonates cause osteoblast apoptosis and inhibit bone nodule formation in vitro. Calcif Tissue Int 82:191–201PubMedCrossRef

75.

Lezcano V, Bellido T, Plotkin LI, Boland R, Morelli S (2012) Role of connexin 43 in the mechanism of action of alendronate: dissociation of anti-apoptotic and proliferative signaling pathways. Arch Biochem Biophys 518:95–102PubMedCentralPubMedCrossRef

76.

Niessen H, Harz H, Bedner P, Kramer K, Willecke K (2000) Selective permeability of different connexin channels to the second messenger inositol 1,4,5-trisphosphate. J Cell Sci 113(pt 8):1365–1372PubMed

77.

Niger C, Luciotti MA, Buo AM, Hebert C, Ma V, Stains JP (2013) The regulation of Runx2 by FGF2 and connexin43 requires the inositol polyphosphate/protein kinase Cdelta cascade. J Bone Miner Res. doi:10.1002/jbmr.1867 PubMed

78.

Jorgensen NR, Geist ST, Civitelli R, Steinberg TH (1997) ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells. J Cell Biol 139:497–506PubMedCrossRef

79.

Jorgensen NR, Henriksen Z, Brot C, Eriksen EF, Sorensen OH, Civitelli R, Steinberg TH (2000) Human osteoblastic cells propagate intercellular calcium signals by two different mechanisms. J Bone Miner Res 15:1024–1032PubMedCrossRef

80.

Yellowley CE, Li Z, Zhou Z, Jacobs CR, Donahue HJ (2000) Functional gap junctions between osteocytic and osteoblastic cells. J Bone Miner Res 15:209–217PubMedCrossRef

81.

Jorgensen NR, Teilmann SC, Henriksen Z, Civitelli R, Sorensen OH, Steinberg TH (2003) Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells. J Biol Chem 278:4082–4086PubMedCrossRef

82.

Huo B, Lu XL, Guo XE (2010) Intercellular calcium wave propagation in linear and circuit-like bone cell networks. Philos Trans A Math Phys Eng Sci 368:617–633PubMedCrossRef

83.

Huo B, Lu XL, Costa KD, Xu Q, Guo XE (2010) An ATP-dependent mechanism mediates intercellular calcium signaling in bone cell network under single cell nanoindentation. Cell Calcium 47:234–241PubMedCentralPubMedCrossRef

84.

Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Hayano S, Balam TA, Naruse K, Yamashiro T (2013) Ex vivo real-time observation of Ca²⁺ signaling in living bone in response to shear stress applied on the bone surface. Bone 53:204–215PubMedCrossRef

85.

Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Kurosaka H, Naruse K, Yamashiro T (2012) In situ imaging of the autonomous intracellular Ca²⁺ oscillations of osteoblasts and osteocytes in bone. Bone 50:842–852PubMedCrossRef

86.

Jing D, Lu XL, Luo E, Sajda P, Leong PL, Guo XE (2013) Spatiotemporal properties of intracellular calcium signaling in osteocytic and osteoblastic cell networks under fluid flow. Bone 53:531–540PubMedCrossRef

87.

Molen MAV, Donahue HJ, Rubin CT, McLeod KJ (2000) Osteoblastic networks with deficient coupling: differential effects of magnetic and electric field exposure. Bone 27:227–231CrossRef

88.

Herve JC, Derangeon M, Sarrouilhe D, Giepmans BN, Bourmeyster N (2012) Gap junctional channels are parts of multiprotein complexes. Biochim Biophys Acta 1818:1844–1865PubMedCrossRef

89.

Herve JC, Bourmeyster N, Sarrouilhe D (2004) Diversity in protein–protein interactions of connexins: emerging roles. Biochim Biophys Acta 1662:22–41PubMedCrossRef

90.

Niger C, Hebert C, Stains JP (2010) Interaction of connexin43 and protein kinase C-delta during FGF2 signaling. BMC Biochem 11:14PubMedCentralPubMedCrossRef

91.

Jorgensen NR, Teilmann SC, Henriksen Z, Meier E, Hansen SS, Jensen JE, Sorensen OH, Petersen JS (2005) 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 146:4745–4754PubMedCrossRef

92.

Axelsen LN, Stahlhut M, Mohammed S, Larsen BD, Nielsen MS, Holstein-Rathlou NH, Andersen S, Jensen ON, Hennan JK, Kjolbye AL (2006) Identification of ischemia-regulated phosphorylation sites in connexin43: a possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123). J Mol Cell Cardiol 40:790–798PubMedCrossRef

93.

Haugan K, Marcussen N, Kjolbye AL, Nielsen MS, Hennan JK, Petersen JS (2006) Treatment with the gap junction modifier rotigaptide (ZP123) reduces infarct size in rats with chronic myocardial infarction. J Cardiovasc Pharmacol 47:236–242PubMedCrossRef

Titel: Molecular Mechanisms of Osteoblast/Osteocyte Regulation by Connexin43
verfasst von: Joseph P. Stains
Marcus P. Watkins
Susan K. Grimston
Carla Hebert
Roberto Civitelli
Publikationsdatum: 01.01.2014
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 1/2014
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-013-9742-6

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