Browse > Article

Skeletal Development - Wnts Are in Control  

Hartmann, Christine (Research Institute of Molecular Pathology)
Publication Information
Molecules and Cells / v.24, no.2, 2007 , pp. 177-184 More about this Journal
Abstract
Approximately 200 individual skeletal elements, which differ in shape and size, are the building blocks of the vertebrate skeleton. Various features of the individual skeletal elements, such as their location, shape, growth and differentiation rate, are being determined during embryonic development. A few skeletal elements, such as the lateral halves of the clavicle and parts of the skull are formed by a process called intramembranous ossification, whereby mesenchymal cells differentiate directly into osteoblasts, while the majority of skeletal elements are formed via endochondral ossification. The latter process starts with the formation of a cartilaginous template, which eventually is being replaced by bone. This requires co-regulation of differentiation of the cell-types specific for cartilage and bone, chondrocytes and osteoblasts, respectively. In recent years it has been demonstrated that Wnt family members and their respective intracellular pathways, such as non-canonical and the canonical $Wnt/{\beta}$-catenin pathway, play important and diverse roles during different steps of vertebrate skeletal development. Based on the recent discoveries modulation of the canonical Wnt-signaling pathway could be an interesting approach to direct stem cells into certain skeletal lineages.
Keywords
Beta-Catenin; Chondrocytes; Differentiation; Hypertrophy; LRP; Osteoblasts; Skeletal Lineage; Wnts;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 18  (Related Records In Web of Science)
연도 인용수 순위
1 Akiyama, H., Lyons, J. P., Mori-Akiyama, Y., Yang, X., Zhang, R., et al. (2004) Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 18, 1072− 1087
2 Baron, R. and Rawadi, G. (2007) Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 148, 2635−243
3 Bodine, P. V., Zhao, W., Kharode, Y. P., Bex, F. J., Lambert, A. J., et al. (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
4 Gaur, T., Rich, L., Lengner, C. J., Hussain, S., Trevant, B., et al. (2006) Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation. J. Cell. Physiol. 208, 87−96
5 Glass, D. A., 2nd, and Karsenty, G. (2006) Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway. Curr. Top Dev. Biol. 73, 43−84
6 Guo, X., Day, T. F., Jiang, X., Garrett-Beal, L., Topol, L., et al. (2004) Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. Genes Dev. 18, 2404−2417
7 Haegel, H., Larue, L., Ohsugi, M., Fedorov, L., Herrenknecht, K., et al. (1995) Lack of beta-catenin affects mouse development at gastrulation. Development 121, 3529−3537
8 Hartmann, C. and Tabin, C. J. (2001) Wnt-14 plays a pivotal role in inducing synovial joint formation in the developing appendicular skeleton. Cell 104, 341−351
9 Hill, T. P., Spater, D., Taketo, M. M., Birchmeier, W., and Hartmann, C. (2005) Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev. Cell 8, 727−738
10 Karsenty, G. and Wagner, E. F. (2002) Reaching a genetic and molecular understanding of skeletal development. Dev. Cell 2, 389−406
11 Kronenberg, H. M. (2003) Developmental regulation of the growth plate. Nature 423, 332−336
12 Lai, L. P. and Mitchell, J. (2005) Indian hedgehog: its roles and regulation in endochondral bone development. J. Cell. Biochem. 96, 1163−1173
13 Li, X., Zhang, Y., Kang, H., Liu, W., Liu, P., et al. (2005b) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 280, 19883−19887   DOI   ScienceOn
14 Ryu, J. H., Kim, S. J., Kim, S. H., Oh, C. D., Hwang, S. G., et al. (2002) Regulation of the chondrocyte phenotype by betacatenin. Development 129, 5541−5550
15 Spater, D., Hill, T. P., Gruber, M., and Hartmann, C. (2006a) Role of canonical Wnt-signalling in joint formation. Eur. Cell. Mater. 12, 71−80
16 Tamamura, Y., Otani, T., Kanatani, N., Koyama, E., Kitagaki, J., et al. (2005) Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J. Biol. Chem. 280, 19185−19195
17 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
18 van der Horst, G., van der Werf, S. M., Farih-Sips, H., van Bezooijen, R. L., Lowik, C. W., et al. (2005) Downregulation of Wnt signaling by increased expression of Dickkopf-1 and -2 is a prerequisite for late-stage osteoblast differentiation of KS483 cells. J. Bone Miner. Res. 20, 1867−77
19 Yang, Y., Topol, L., Lee, H., and Wu, J. (2003) Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development 130, 1003− 1015
20 Yamaguchi, T. P., Bradley, A., McMahon, A. P., and Jones, S. (1999) A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126, 1211− 1223
21 Bi, W., Huang, W., Whitworth, D. J., Deng, J. M., Zhang, Z., et al. (2001) Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization. Proc. Natl. Acad. Sci. USA 98, 6698−6703
22 Glass, D. A., 2nd, Bialek, P., Ahn, J. D., Starbuck, M., Patel, M. S., et al. (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev. Cell 8, 751−764
23 Hartmann, C. (2006) A Wnt canon orchestrating osteoblastogenesis. Trends Cell Biol. 16, 151-158   DOI   ScienceOn
24 Tufan, A. C. and Tuan, R. S. (2001) Wnt regulation of limb mesenchymal chondrogenesis is accompanied by altered Ncadherin- related functions. FASEB J. 15, 1436−1438
25 Wagner, E. F. and Karsenty, G. (2001) Genetic control of skeletal development. Curr. Opin. Genet. Dev. 11, 527−532
26 Hu, H., Hilton, M. J., Tu, X., Yu, K., Ornitz, D. M., et al. (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132, 49−60
27 Jin, E. J., Park, J. H., Lee, S. Y., Chun, J. S., Bang, O. S., et al. (2006) Wnt-5a is involved in TGF-beta3-stimulated chondrogenic differentiation of chick wing bud mesenchymal cells. Int. J. Biochem. Cell Biol. 38, 183−195
28 Lee, N. K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J. D., et al. (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130, 456−469
29 Li, X., Liu, P., Liu, W., Maye, P., Zhang, J., et al. (2005a) Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat. Genet. 37, 945−952
30 Rudnicki, J. A. and Brown, A. M. (1997) Inhibition of chondrogenesis by Wnt gene expression in vivo and in vitro. Dev. Biol. 185, 104−118
31 Clement-Lacroix, P., Ai, M., Morvan, F., Roman-Roman, S., Vayssiere, B., et al. (2005) Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc. Natl. Acad. Sci. USA 102, 17406− 17411
32 Archer, C. W., Dowthwaite, G. P., and Francis-West, P. (2003) Development of synovial joints. Birth Defects Res. C Embryo Today 69, 144−155
33 Church, V., Nohno, T., Linker, C., Marcelle, C., and Francis- West, P. (2002) Wnt regulation of chondrocyte differentiation. J. Cell Sci. 115, 4809−4818
34 St-Jacques, B., Hammerschmidt, M., and McMahon, A. P. (1999) Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev. 13, 2072−2086
35 Kawakami, Y., Wada, N., Nishimatsu, S. I., Ishikawa, T., Noji, S., et al. (1999) Involvement of Wnt-5a in chondrogenic pattern formation in the chick limb bud. Dev. Growth Differ. 41, 29−40
36 Hwang, S. G., Ryu, J. H., Kim, I. C., Jho, E. H., Jung, H. C., et al. (2004) Wnt-7a causes loss of differentiated phenotype and inhibits apoptosis of articular chondrocytes via different mechanisms. J. Biol. Chem. 279, 26597−26604
37 MacDonald, B. T., Joiner, D. M., Oyserman, S. M., Sharma, P., Goldstein, S. A., et al. (2007) Bone mass is inversely proportional to Dkk1 levels in mice. Bone 41, 331−339
38 Morvan, F., Boulukos, K., Clement-Lacroix, P., Roman Roman, S., Suc-Royer, I., et al. (2006) Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J. Bone Miner. Res. 21, 934−945
39 Spater, D., Hill, T. P., O'Sullivan R, J., Gruber, M., Conner, D. A., et al. (2006b) Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis. Development 133, 3039−3049
40 Tufan, A. C., Daumer, K. M., DeLise, A. M., and Tuan, R. S. (2002) AP-1 transcription factor complex is a target of signals from both WnT-7a and N-cadherin-dependent cell-cell adhesion complex during the regulation of limb mesenchymal chondrogenesis. Exp. Cell Res. 273, 197−203
41 Balemans, W. and Van Hul, W. (2007) The genetics of lowdensity lipoprotein receptor-related protein 5 in bone: a story of extremes. Endocrinology 148, 2622−2629
42 Chang, J., Sonoyama, W., Wang, Z., Jin, Q., Zhang, C., et al. (2007) Non-canonical WNT-4 signaling enhances bone regeneration of mesenchymal stem cells in craniofacial defects through activation of p38 MAPK. J. Biol. Chem. 282, 30938- 30948   DOI   ScienceOn
43 Hartmann, C. and Tabin, C. J. (2000) Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 127, 3141−3159
44 Baron, R., Rawadi, G., and Roman-Roman, S. (2006) Wnt signaling: a key regulator of bone mass. Curr. Top Dev. Biol. 76, 103−127
45 Day, T. F., Guo, X., Garrett-Beal, L., and Yang, Y. (2005) Wnt/ beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev. Cell 8, 739−750
46 Kim, J. B., Leucht, P., Lam, K., Luppen, C., Ten Berge, D., et al. (2007) Bone regeneration is regulated by Wnt signaling. J. Bone Miner. Res. [Epub ahead of print]
47 Krishnan, V., Bryant, H. U., and Macdougald, O. A. (2006) Regulation of bone mass by Wnt signaling. J. Clin. Invest. 116, 1202−1209
48 Moser, A. R., Shoemaker, A. R., Connelly, C. S., Clipson, L., Gould, K. A., et al. (1995) Homozygosity for the Min allele of Apc results in disruption of mouse development prior to gastrulation. Dev. Dyn. 203, 422−433
49 Ryu, J. H. and Chun, J. S. (2006) Opposing roles of WNT-5A and WNT-11 in interleukin-1beta regulation of type II collagen expression in articular chondrocytes. J. Biol. Chem. 281, 22039−22047
50 Kronenberg, H. M. (2006) PTHrP and skeletal development. Ann. NY Acad. Sci. 1068, 1−13
51 Rountree, R. B., Schoor, M., Chen, H., Marks, M. E., Harley, V., et al. (2004) BMP receptor signaling is required for postnatal maintenance of articular cartilage. PLoS Biol. 2, e355   DOI
52 Rawadi, G. and Roman-Roman, S. (2005) Wnt signalling pathway: a new target for the treatment of osteoporosis. Expert Opin. Ther. Targets 9, 1063−1077
53 Rodda, S. J. and McMahon, A. P. (2006) Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133, 3231−3244
54 Enomoto-Iwamoto, M., Kitagaki, J., Koyama, E., Tamamura, Y., Wu, C., et al. (2002) The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis. Dev. Biol. 251, 142−156
55 Bodine, P. V. and Komm, B. S. (2006) Wnt signaling and osteoblastogenesis. Rev. Endocr. Metab. Disord. 7, 33−39
56 de Crombrugghe, B., Lefebvre, V., Behringer, R. R., Bi, W., Murakami, S., et al. (2000) Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol. 19, 389−394
57 Gaur, T., Lengner, C. J., Hovhannisyan, H., Bhat, R. A., Bodine, P. V., et al. (2005) Canonical WNT signaling promotes osteogenesis by directly stimulating RUNX2 gene expression. J. Biol. Chem. 280, 33132−33140
58 Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., et al. (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107, 513−523
59 Huelsken, J., Vogel, R., Brinkmann, V., Erdmann, B., Birchmeier, C., et al. (2000) Requirement for beta-catenin in anteriorposterior axis formation in mice. J. Cell Biol. 148, 567−578
60 Hwang, S. G., Yu, S. S., Lee, S. W., and Chun, J. S. (2005a) Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway. FEBS Lett. 579, 4837−4842
61 Mak, K. K., Chen, M. H., Day, T. F., Chuang, P. T., and Yang, Y. (2006) Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development 133, 3695−3707
62 Chen, Y., Whetstone, H. C., Lin, A. C., Nadesan, P., Wei, Q., et al. (2007) Beta-catenin signaling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing. PLoS Med. 4, e249
63 Hens, J. R., Wilson, K. M., Dann, P., Chen, X., Horowitz, M. C., et al. (2005) TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro. J. Bone Miner. Res. 20, 1103−1113
64 Bi, W., Deng, J. M., Zhang, Z., Behringer, R. R., and de Crombrugghe, B. (1999) Sox9 is required for cartilage formation. Nat. Genet. 22, 85−89
65 Daumer, K. M., Tufan, A. C., and Tuan, R. S. (2004) Long-term in vitro analysis of limb cartilage development: involvement of Wnt signaling. J. Cell. Biochem. 93, 526−541
66 Tu, X., Joeng, K. S., Nakayama, K. I., Nakayama, K., Rajagopal, J., et al. (2007) Noncanonical Wnt signaling through G protein- linked PKCdelta activation promotes bone formation. Dev. Cell 12, 113−127
67 Hwang, S. G., Yu, S. S., Ryu, J. H., Jeon, H. B., Yoo, Y. J., et al. (2005b) Regulation of beta-catenin signaling and maintenance of chondrocyte differentiation by ubiquitin-independent proteasomal degradation of alpha-catenin. J. Biol. Chem. 280, 12758−12765
68 Johnson, M. L., Harnish, K., Nusse, R., and Van Hul, W. (2004) LRP5 and Wnt signaling: a union made for bone. J. Bone Miner. Res. 19, 1749−1757
69 Westendorf, J. J., Kahler, R. A., and Schroeder, T. M. (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341, 19−39
70 Logan, C. Y. and Nusse, R. (2004) The Wnt signaling pathway in development and disease. Annu. Rev. Cell. Dev. Biol. 20, 781−810