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Article

Osteocyte Wnt/β-Catenin Signaling Is Required for Normal Bone Homeostasis

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Pages 3071-3085 | Received 30 Oct 2009, Accepted 05 Apr 2010, Published online: 20 Mar 2023

REFERENCES

  • Aguirre, J. I., L. I. Plotkin, S. A. Stewart, R. S. Weinstein, A. M. Parfitt, S. C. Manolagas, and T. Bellido. 2006. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J. Bone Miner. Res. 21:605–615.
  • Almeida, M., L. Han, M. Martin-Millan, C. A. O'Brien, and S. C. Manolagas. 2007. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J. Biol. Chem. 282:27298–27305.
  • Armstrong, V. J., M. Muzylak, A. Sunters, G. Zaman, L. K. Saxon, J. S. Price, and L. E. Lanyon. 2007. Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J. Biol. Chem. 282:20715–20727.
  • Babij, P., W. Zhao, C. Small, Y. Kharode, P. J. Yaworsky, M. L. Bouxsein, P. S. Reddy, P. V. Bodine, J. A. Robinson, B. Bhat, J. Marzolf, R. A. Moran, and F. Bex. 2003. High bone mass in mice expressing a mutant LRP5 gene. J. Bone Miner. Res. 18:960–974.
  • Bennett, C. N., H. Ouyang, Y. L. Ma, Q. Zeng, I. Gerin, K. M. Sousa, T. F. Lane, V. Krishnan, K. D. Hankenson, and O. A. MacDougald. 2007. Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation. J. Bone Miner. Res. 22:1924–1932.
  • Benson, M. D., J. E. Aubin, G. Xiao, P. E. Thomas, and R. T. Franceschi. 1999. Cloning of a 2.5 kb murine bone sialoprotein promoter fragment and functional analysis of putative Osf2 binding sites. J. Bone Miner. Res. 14:396–405.
  • Bodine, P. V., W. Zhao, Y. P. Kharode, F. J. Bex, A. J. Lambert, M. B. Goad, T. Gaur, G. S. Stein, J. B. Lian, and B. S. Komm. 2004. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol. Endocrinol. 18:1222–1237.
  • Bonewald, L. F. 2005. Generation and function of osteocyte dendritic processes. J. Musculoskelet. Neuronal Interact. 5:321–324.
  • Bonewald, L. F. 2006. Mechanosensation and transduction in osteocytes. Bonekey Osteovision 3:7–15.
  • Bonewald, L. F. 2007. Osteocytes as dynamic multifunctional cells. Ann. N. Y. Acad. Sci. 1116:281–290.
  • Bonewald, L. F., and M. L. Johnson. 2008. Osteocytes, mechanosensing and Wnt signaling. Bone 42:606–615.
  • Boyce, B. F., and L. Xing. 2008. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch. Biochem. Biophys. 473:139–146.
  • Brault, V., R. Moore, S. Kutsch, M. Ishibashi, D. H. Rowitch, A. P. McMahon, L. Sommer, O. Boussadia, and R. Kemler. 2001. Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128:1253–1264.
  • Breuil, V., H. Schmid-Antomarchi, A. Schmid-Alliana, R. Rezzonico, L. Euller-Ziegler, and B. Rossi. 2003. The receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) is a new chemotactic factor for human monocytes. FASEB J. 17:1751–1753.
  • Bucay, N., I. Sarosi, C. R. Dunstan, S. Morony, J. Tarpley, C. Capparelli, S. Scully, H. L. Tan, W. Xu, D. L. Lacey, W. J. Boyle, and W. S. Simonet. 1998. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 12:1260–1268.
  • Cardoso, L., B. C. Herman, O. Verborgt, D. Laudier, R. J. Majeska, and M. B. Schaffler. 2009. Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue. J. Bone Miner. Res. 24:597–605.
  • Caverzasio, J. 2009. Non-canonical Wnt signaling: what is its role in bone? Bonekey 6:107–115.
  • Day, T. F., X. Guo, L. Garrett-Beal, and Y. Yang. 2005. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev. Cell 8:739–750.
  • Glass, D. A., II, P. Bialek, J. D. Ahn, M. Starbuck, M. S. Patel, H. Clevers, M. M. Taketo, F. Long, A. P. McMahon, R. A. Lang, and G. Karsenty. 2005. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev. Cell 8:751–764.
  • Gu, G., M. Mulari, Z. Peng, T. A. Hentunen, and H. K. Vaananen. 2005. Death of osteocytes turns off the inhibition of osteoclasts and triggers local bone resorption. Biochem. Biophys. Res. Commun. 335:1095–1101.
  • Gu, G., M. Nars, T. A. Hentunen, K. Metsikko, and H. K. Vaananen. 2006. Isolated primary osteocytes express functional gap junctions in vitro. Cell Tissue Res. 323:263–271.
  • Hedgecock, N. L., T. Hadi, A. A. Chen, S. B. Curtiss, R. B. Martin, and S. J. Hazelwood. 2007. Quantitative regional associations between remodeling, modeling, and osteocyte apoptosis and density in rabbit tibial midshafts. Bone 40:627–637.
  • Heino, T. J., T. A. Hentunen, and H. K. Vaananen. 2004. Conditioned medium from osteocytes stimulates the proliferation of bone marrow mesenchymal stem cells and their differentiation into osteoblasts. Exp. Cell Res. 294:458–468.
  • Henriksen, K., A. V. Neutzsky-Wulff, L. F. Bonewald, and M. A. Karsdal. 2009. Local communication on and within bone controls bone remodeling. Bone 44:1026–1033.
  • Hill, T. P., D. Spater, M. M. Taketo, W. Birchmeier, and C. Hartmann. 2005. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev. Cell 8:727–738.
  • Holmen, S. L., C. R. Zylstra, A. Mukherjee, R. E. Sigler, M. C. Faugere, M. L. Bouxsein, L. Deng, T. L. Clemens, and B. O. Williams. 2005. Essential role of beta-catenin in postnatal bone acquisition. J. Biol. Chem. 280:21162–21168.
  • Hu, H., M. J. Hilton, X. Tu, K. Yu, D. M. Ornitz, and F. Long. 2005. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49–60.
  • Inouye, M. 1976. Differential staining of cartilage and bone in fetal mouse skeleton by alcian blue and alizarin red-S. Congen. Anom. 16:171–173.
  • Jho, E. H., T. Zhang, C. Domon, C. K. Joo, J. N. Freund, and F. Costantini. 2002. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell. Biol. 22:1172–1183.
  • Kamioka, H., T. Honjo, and T. Takano-Yamamoto. 2001. A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interference contrast microscopy. Bone 28:145–149.
  • Kato, M., M. S. Patel, R. Levasseur, I. Lobov, B. H. Chang, D. A. Glass II, C. Hartmann, L. Li, T. H. Hwang, C. F. Brayton, R. A. Lang, G. Karsenty, and L. Chan. 2002. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J. Cell Biol. 157:303–314.
  • Keller, H., and M. Kneissel. 2005. SOST is a target gene for PTH in bone. Bone 37:148–158.
  • Kneissel, M., A. Boyde, and J. A. Gasser. 2001. Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34). Bone 28:237–250.
  • Kurata, K., T. J. Heino, H. Higaki, and H. K. Vaananen. 2006. Bone marrow cell differentiation induced by mechanically damaged osteocytes in 3D gel-embedded culture. J. Bone Miner. Res. 21:616–625.
  • Lam, J., C. A. Nelson, F. P. Ross, S. L. Teitelbaum, and D. H. Fremont. 2001. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity. J. Clin. Invest. 108:971–979.
  • Leung, J. Y., F. T. Kolligs, R. Wu, Y. Zhai, R. Kuick, S. Hanash, K. R. Cho, and E. R. Fearon. 2002. Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling. J. Biol. Chem. 277:21657–21665.
  • Li, X., M. S. Ominsky, Q. T. Niu, N. Sun, B. Daugherty, D. D'Agostin, C. Kurahara, Y. Gao, J. Cao, J. Gong, F. Asuncion, M. Barrero, K. Warmington, D. Dwyer, M. Stolina, S. Morony, I. Sarosi, P. J. Kostenuik, D. L. Lacey, W. S. Simonet, H. Z. Ke, and C. Paszty. 2008. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J. Bone Miner. Res. 23:860–869.
  • Liang, M., G. Russell, and P. A. Hulley. 2008. Bim, Bak, and Bax regulate osteoblast survival. J. Bone Miner. Res. 23:610–620.
  • Lin, C., X. Jiang, Z. Dai, X. Guo, T. Weng, J. Wang, Y. Li, G. Feng, X. Gao, and L. He. 2009. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J. Bone Miner. Res. 24:1651–1661.
  • Liu, F., S. Kohlmeier, and C. Y. Wang. 2008. Wnt signaling and skeletal development. Cell Signal. 20:999–1009.
  • Liu, X. H., A. Kirschenbaum, S. Yao, and A. C. Levine. 2007. Androgens promote preosteoblast differentiation via activation of the canonical Wnt signaling pathway. Ann. N. Y. Acad. Sci. 1116:423–431.
  • Lu, Y., Y. Xie, S. Zhang, V. Dusevich, L. F. Bonewald, and J. Q. Feng. 2007. DMP1-targeted Cre expression in odontoblasts and osteocytes. J. Dent. Res. 86:320–325.
  • Lustig, B., B. Jerchow, M. Sachs, S. Weiler, T. Pietsch, U. Karsten, M. van de Wetering, H. Clevers, P. M. Schlag, W. Birchmeier, and J. Behrens. 2002. Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol. Cell. Biol. 22:1184–1193.
  • Manolagas, S. C., and M. Almeida. 2007. Gone with the Wnts: beta-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism. Mol. Endocrinol. 21:2605–2614.
  • Martin, R. B. 2000. Does osteocyte formation cause the nonlinear refilling of osteons? Bone 26:71–78.
  • Martin, T., J. H. Gooi, and N. A. Sims. 2009. Molecular mechanisms in coupling of bone formation to resorption. Crit. Rev. Eukaryot. Gene Expr. 19:73–88.
  • Mbalaviele, G., C. S. Shin, and R. Civitelli. 2006. Cell-cell adhesion and signaling through cadherins: connecting bone cells in their microenvironment. J. Bone Miner. Res. 21:1821–1827.
  • Mizuno, A., N. Amizuka, K. Irie, A. Murakami, N. Fujise, T. Kanno, Y. Sato, N. Nakagawa, H. Yasuda, S. Mochizuki, T. Gomibuchi, K. Yano, N. Shima, N. Washida, E. Tsuda, T. Morinaga, K. Higashio, and H. Ozawa. 1998. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem. Biophys. Res. Commun. 247:610–615.
  • Noble, B. S., N. Peet, H. Y. Stevens, A. Brabbs, J. R. Mosley, G. C. Reilly, J. Reeve, T. M. Skerry, and L. E. Lanyon. 2003. Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am. J. Physiol. Cell Physiol. 284:C934–C943.
  • Noh, T., Y. Gabet, J. Cogan, Y. Shi, A. Tank, T. Sasaki, B. Criswell, A. Dixon, C. Lee, J. Tam, T. Kohler, E. Segev, L. Kockeritz, J. Woodgett, R. Muller, Y. Chai, E. Smith, I. Bab, and B. Frenkel. 2009. Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. PLoS One 4:e5438.
  • Onyia, J. E., R. R. Miles, X. Yang, D. L. Halladay, J. Hale, A. Glasebrook, D. McClure, G. Seno, L. Churgay, S. Chandrasekhar, and T. J. Martin. 2000. In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene. J. Bone Miner. Res. 15:863–871.
  • Paic, F., J. C. Igwe, R. Nori, M. S. Kronenberg, T. Franceschetti, P. Harrington, L. Kuo, D. G. Shin, D. W. Rowe, S. E. Harris, and I. Kalajzic. 2009. Identification of differentially expressed genes between osteoblasts and osteocytes. Bone 45:682–692.
  • Parfitt, A. M., M. K. Drezner, F. H. Glorieux, J. A. Kanis, H. Malluche, P. J. Meunier, S. M. Ott, and R. R. Recker. 1987. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J. Bone Miner. Res. 2:595–610.
  • Pederson, L., M. Ruan, J. J. Westendorf, S. Khosla, and M. J. Oursler. 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.
  • Piters, E., E. Boudin, and W. Van Hul. 2008. Wnt signaling: a win for bone. Arch. Biochem. Biophys. 473:112–116.
  • Robinson, J. A., M. Chatterjee-Kishore, P. J. Yaworsky, D. M. Cullen, W. Zhao, C. Li, Y. Kharode, L. Sauter, P. Babij, E. L. Brown, A. A. Hill, M. P. Akhter, M. L. Johnson, R. R. Recker, B. S. Komm, and F. J. Bex. 2006. Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J. Biol. Chem. 281:31720–31728.
  • Robling, A. G., P. J. Niziolek, L. A. Baldridge, K. W. Condon, M. R. Allen, I. Alam, S. M. Mantila, J. Gluhak-Heinrich, T. M. Bellido, S. E. Harris, and C. H. Turner. 2008. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J. Biol. Chem. 283:5866–5875.
  • Sawakami, K., A. G. Robling, M. Ai, N. D. Pitner, D. Liu, S. J. Warden, J. Li, P. Maye, D. W. Rowe, R. L. Duncan, M. L. Warman, and C. H. Turner. 2006. The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J. Biol. Chem. 281:23698–23711.
  • Shah, S., A. Hecht, R. Pestell, and S. W. Byers. 2003. Trans-repression of beta-catenin activity by nuclear receptors. J. Biol. Chem. 278:48137–48145.
  • Tami, A. E., M. B. Schaffler, and M. L. Knothe Tate. 2003. Probing the tissue to subcellular level structure underlying bone's molecular sieving function. Biorheology 40:577–590.
  • Tatsumi, S., K. Ishii, N. Amizuka, M. Li, T. Kobayashi, K. Kohno, M. Ito, S. Takeshita, and K. Ikeda. 2007. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 5:464–475.
  • Toyosawa, S., S. Shintani, T. Fujiwara, T. Ooshima, A. Sato, N. Ijuhin, and T. Komori. 2001. Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts. J. Bone Miner. Res. 16:2017–2026.
  • Vaananen, H. K., and T. Laitala-Leinonen. 2008. Osteoclast lineage and function. Arch. Biochem. Biophys. 473:132–138.
  • van Bezooijen, R. L., B. A. Roelen, A. Visser, L. van der Wee-Pals, E. de Wilt, M. Karperien, H. Hamersma, S. E. Papapoulos, P. ten Dijke, and C. W. Lowik. 2004. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J. Exp. Med. 199:805–814.
  • Verborgt, O., N. A. Tatton, R. J. Majeska, and M. B. Schaffler. 2002. Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation? J. Bone Miner. Res. 17:907–914.
  • Wang, L., C. Ciani, S. B. Doty, and S. P. Fritton. 2004. Delineating bone's interstitial fluid pathway in vivo. Bone 34:499–509.
  • Weinbaum, S., S. C. Cowin, and Y. Zeng. 1994. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J. Biomech. 27:339–360.
  • Winkler, D. G., M. K. Sutherland, J. C. Geoghegan, C. Yu, T. Hayes, J. E. Skonier, D. Shpektor, M. Jonas, B. R. Kovacevich, K. Staehling-Hampton, M. Appleby, M. E. Brunkow, and J. A. Latham. 2003. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 22:6267–6276.
  • Yan, Y., D. Tang, M. Chen, J. Huang, R. Xie, J. H. Jonason, X. Tan, W. Hou, D. Reynolds, W. Hsu, S. E. Harris, J. E. Puzas, H. Awad, R. J. O'Keefe, B. F. Boyce, and D. Chen. 2009. Axin2 controls bone remodeling through the β-catenin-BMP signaling pathway in adult mice. J. Cell Sci. 122:3566–3578.
  • Yochum, G. S., S. McWeeney, V. Rajaraman, R. Cleland, S. Peters, and R. H. Goodman. 2007. Serial analysis of chromatin occupancy identifies beta-catenin target genes in colorectal carcinoma cells. Proc. Natl. Acad. Sci. U. S. A. 104:3324–3329.
  • You, L., S. Temiyasathit, P. Lee, C. H. Kim, P. Tummala, W. Yao, W. Kingery, A. M. Malone, R. Y. Kwon, and C. R. Jacobs. 2008. Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone 42:172–179.
  • Zaman, G., H. L. Jessop, M. Muzylak, R. L. De Souza, A. A. Pitsillides, J. S. Price, and L. L. Lanyon. 2006. Osteocytes use estrogen receptor alpha to respond to strain but their ERalpha content is regulated by estrogen. J. Bone Miner. Res. 21:1297–1306.
  • Zhao, S., Y. K. Zhang, S. Harris, S. S. Ahuja, and L. F. Bonewald. 2002. MLO-Y4 osteocyte-like cells support osteoclast formation and activation. J. Bone Miner. Res. 17:2068–2079.

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