Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation

Nature Communications

Volumn 7, Issue , 2016, Pages

  Yuan, Xue ^a   Cao, Jay ^b   He, Xiaoning ^a   Serra, Rosa ^c   Qu, Jun ^a   Cao, Xu ^d   Yang, Shuying ^a  

^a UNIVERSITY AT BUFFALO   (United States)

^b GRAND FORKS HUMAN NUTRITION RESEARCH CENTER   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; CYTOCHALASIN D; F ACTIN; INTRAFLAGELLAR TRANSPORT PROTEIN 80; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; UNCLASSIFIED DRUG; CARRIER PROTEIN; IFT80 PROTEIN, MOUSE; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN;

BONE; CELLS AND CELL COMPONENTS; DIFFERENTIATION; GROWTH; OSTEOLOGY; PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BONE MASS; CELL DIFFERENTIATION; CONTROLLED STUDY; CRANIOFACIAL MALFORMATION; EUKARYOTIC FLAGELLUM; FEMALE; GROWTH RETARDATION; MALE; MOUSE; NONHUMAN; OSTEOBLAST; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; SKELETON MALFORMATION; ANIMAL; BONE DEVELOPMENT; CILIUM; CYTOLOGY; GENE DELETION; KNOCKOUT MOUSE; METABOLIC BONE DISEASE; METABOLISM; ORGANOGENESIS; PATHOLOGY; STEM CELL; STRESS FIBER;

ERINACEIDAE; MUS;

ANIMALS; BONE DISEASES, METABOLIC; CARRIER PROTEINS; CELL DIFFERENTIATION; CILIA; GENE DELETION; HEDGEHOG PROTEINS; MICE, KNOCKOUT; ORGANOGENESIS; OSTEOBLASTS; OSTEOGENESIS; RHOA GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION; STEM CELLS; STRESS FIBERS;

EID: 84961730194     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms11024     Document Type: Article

References (70)

1. Singla, V., Reiter, J. F. The primary cilium as the cell's antenna: signalling at a sensory organelle. Science 313, 629-633 (2006).
2. Jackson, P. K. Do cilia put brakes on the cell cycle Nat. Cell Biol. 13, 340-342 (2011).
3. Goetz, S. C., Anderson, K. V. The primary cilium: a signalling centre during vertebrate development. Nat. Rev. Genet. 11, 331-344 (2010).
4. Xiao, Z. et al. Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J. Biol. Chem. 281, 30884-30895 (2006).
5. Yuan, X., Yang, S. Cilia/Ift protein and motor-related bone diseases and mouse models. Front. Biosci. 20, 515-555 (2015).
6. Hoey, D. A., Kelly, D. J., Jacobs, C. R. A role for the primary cilium in paracrine signalling between mechanically stimulated osteocytes and mesenchymal stem cells. Biochem. Biophys. Res. Commun. 412, 182-187 (2011).
7. Malone, A. M. et al. Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc. Natl Acad. Sci. USA 104, 13325-13330 (2007).
8. Temiyasathit, S. et al. Mechanosensing by the primary cilium: deletion of Kif3A reduces bone formation due to loading. PLoS ONE 7, e33368 (2012).
9. Temiyasathit, S., Jacobs, C. R. Osteocyte primary cilium and its role in bone mechanotransduction. Ann. NY Acad. Sci. 1192, 422-428 (2010).
10. Qiu, N. et al. Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia. J. Cell Sci. 125, 1945-1957 (2012).
11. Xiao, Z. et al. Conditional disruption of Pkd1 in osteoblasts results in osteopenia due to direct impairment of bone formation. J. Biol. Chem. 285, 1177-1187 (2010).
12. Xiao, Z. et al. Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice. FASEB J. 25, 2418-2432 (2011).
13. Friedland-Little, J. M. et al. A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus. Hum. Mol. Genet. 20, 3725-3737 (2011).
14. Huangfu, D. et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83-87 (2003).
15. Haycraft, C. J. et al. Intraflagellar transport is essential for endochondral bone formation. Development 134, 307-316 (2007).
16. Ocbina, P. J., Eggenschwiler, J. T., Moskowitz, I., Anderson, K. V. Complex interactions between genes controlling trafficking in primary cilia. Nat. Genet. 43, 547-553 (2011).
17. Karp, S. J. et al. Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and-independent pathways. Development 127, 543-548 (2000).
18. Goetz, S. C., Ocbina, P. J., Anderson, K. V. The primary cilium as a Hedgehog signal transduction machine. Methods Cell Biol. 94, 199-222 (2009).
19. Yuan, X., Serra, R. A., Yang, S. Function and regulation of primary cilia and intraflagellar transport proteins in the skeleton. Ann. NY Acad. Sci. 1335, 78-99 (2015).
20. Yamaguchi, A., Komori, T., Suda, T. Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocrine Rev. 21, 393-411 (2000).
21. Shimoyama, A. et al. Ihh/Gli2 signalling promotes osteoblast differentiation by regulating Runx2 expression and function. Mol. Biol. Cell 18, 2411-2418 (2007).
22. Takarada, T. et al. An analysis of skeletal development in osteoblast-specific and chondrocyte-specific runt-related transcription factor-2 (Runx2) knockout mice. J. Bone Mineral Res. 28, 2064-2069 (2013).
23. Kugimiya, F. et al. Involvement of endogenous bone morphogenetic protein (BMP) 2 and BMP6 in bone formation. J. Biol. Chem. 280, 35704-35712 (2005).
24. Shi, Y., Chen, J., Karner, C. M., Long, F. Hedgehog signalling activates a positive feedback mechanism involving insulin-like growth factors to induce osteoblast differentiation. Proc. Natl Acad. Sci. USA 112, 4678-4683 (2015).
25. Chiang, C. et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407-413 (1996).
26. Jenkins, D. Hedgehog signalling: emerging evidence for non-canonical pathways. Cell. Signal. 21, 1023-1034 (2009).
27. Brennan, D., Chen, X., Cheng, L., Mahoney, M., Riobo, N. A. Noncanonical Hedgehog signalling. Vitam. Horm. 88, 55-72 (2012).
28. Riobo, N. A., Saucy, B., Dilizio, C., Manning, D. R. Activation of heterotrimeric G proteins by Smoothened. Proc. Natl Acad. Sci. USA 103, 12607-12612 (2006).
29. Polizio, A. H. et al. Heterotrimeric Gi proteins link Hedgehog signalling to activation of Rho small GTPases to promote fibroblast migration. J. Biol. Chem. 286, 19589-19596 (2011).
30. Chinchilla, P., Xiao, L., Kazanietz, M. G., Riobo, N. A. Hedgehog proteins activate pro-angiogenic responses in endothelial cells through non-canonical signalling pathways. Cell Cycle 9, 570-579 (2010).
31. Beales, P. L. et al. IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat. Genet. 39, 727-729 (2007).
32. Cavalcanti, D. P. et al. Mutation in IFT80 in a fetus with the phenotype of Verma-Naumoff provides molecular evidence for Jeune-Verma-Naumoff dysplasia spectrum. J. Med. Genet. 48, 88-92 (2011).
33. Dagoneau, N. et al. DYNC2H1 mutations cause asphyxiating thoracic dystrophy and short rib-polydactyly syndrome, type III. Am. J. Hum. Genet. 84, 706-711 (2009).
34. Yang, S., Wang, C. The intraflagellar transport protein IFT80 is required for cilia formation and osteogenesis. Bone 51, 407-417 (2012).
35. Rodda, S. J., McMahon, A. P. Distinct roles for Hedgehog and canonical Wnt signalling in specification, differentiation and maintenance of osteoblast progenitors. Development 133, 3231-3244 (2006).
36. Chen, J. C., Jacobs, C. R. Mechanically induced osteogenic lineage commitment of stem cells. Stem Cell Res. Ther. 4, 107 (2013).
37. Etienne-Manneville, S., Hall, A. Rho GTPases in cell biology. Nature 420, 629-635 (2002).
38. Rohatgi, R., Milenkovic, L., Corcoran, R. B., Scott, M. P. Hedgehog signal transduction by Smoothened: pharmacologic evidence for a 2-step activation process. Proc. Natl Acad. Sci. USA 106, 3196-3201 (2009).
39. Wilson, C. W., Chen, M.-H., Chuang, P.-T. Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS ONE 4, e5182 (2009).
40. Julian, L., Olson, M. F. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases 5, e29846 (2014).
41. Pritchard, C. A. et al. B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibres in fibroblasts. Mol. Cell. Biol. 24, 5937-5952 (2004).
42. Kim, J. et al. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature 464, 1048-1051 (2010).
43. Yao, X., Peng, R., Ding, J. Effects of aspect ratios of stem cells on lineage commitments with and without induction media. Biomaterials 34, 930-939 (2013).
44. Kim, J. et al. Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking. Nat. Commun. 6, 6781 (2015).
45. Sharma, N., Kosan, Z. A., Stallworth, J. E., Berbari, N. F., Yoder, B. K. Soluble levels of cytosolic tubulin regulate ciliary length control. Mol. Biol. Cell 22, 806-816 (2011).
46. Yan, X., Zhu, X. Branched F-actin as a negative regulator of cilia formation. Exp. Cell Res. 319, 147-151 (2013).
47. Rix, S., Calmont, A., Scambler, P. J., Beales, P. L. An Ift80 mouse model of short rib polydactyly syndromes shows defects in hedgehog signalling without loss or malformation of cilia. Hum. Mol. Genet. 20, 1306-1314 (2011).
48. Yuan, X., Yang, S. Deletion of IFT80 impairs epiphyseal and articular cartilage formation due to disruption of chondrocyte differentiation. PLoS ONE 10, e0130618 (2015).
49. Wang, C., Yuan, X., Yang, S. IFT80 is essential for chondrocyte differentiation by regulating Hedgehog and Wnt signalling pathways. Exp. Cell Res. 319, 623-632 (2013).
50. Bijlsma,M. F., Borensztajn, K. S., Roelink, H., Peppelenbosch, M. P., Spek, C. A. Sonic hedgehog induces transcription-independent cytoskeletal rearrangement and migration regulated by arachidonate metabolites. Cell. Signal. 19, 2596-2604 (2007).
51. Polizio, A. H., Chinchilla, P., Chen, X., Manning, D. R., Riobo, N. A. Sonic Hedgehog activates the GTPases Rac1 and RhoA in a Gli-independent manner through coupling of smoothened to Gi proteins. Sci. Signal. 4, pt7 (2011).
52. Razumilava, N. et al. Non-canonical Hedgehog signalling contributes to chemotaxis in cholangiocarcinoma. J. Hepatol. 60, 599-605 (2014).
53. Negishi-Koga, T. et al. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat. Med. 17, 1473-1480 (2011).
54. Siegert, P. et al. Pasteurella multocida toxin prevents osteoblast differentiation by transactivation of the MAP-kinase cascade via the Galpha(q/11)-p63RhoGEF-RhoA axis. PLoS Pathog. 9, e1003385 (2013).
55. Hagihara, M. et al. Neogenin, a receptor for bone morphogenetic proteins. J. Biol. Chem. 286, 5157-5165 (2011).
56. Yoshikawa, H., Yoshioka, K., Nakase, T., Itoh, K. Stimulation of ectopic bone formation in response to BMP-2 by Rho kinase inhibitor: a pilot study. Clin. Orthopaed. Relat Res. 467, 3087-3095 (2009).
57. Prowse, P. D., Elliott, C. G., Hutter, J., Hamilton, D. W. Inhibition of Rac and ROCK signalling influence osteoblast adhesion, differentiation and mineralization on titanium topographies. PLoS ONE 8, e58898 (2013).
58. Cao, J. et al. miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics. Nat. Cell Biol. 14, 697-706 (2012).
59. Sanchez de Diego, A., Alonso Guerrero, A., Martnez-A, C., van Wely, K. H. M. Dido3-dependent HDAC6 targeting controls cilium size. Nat. Commun. 5, 3500 (2014).
60. Higuchi, C., Nakamura, N., Yoshikawa, H., Itoh, K. Transient dynamic actin cytoskeletal change stimulates the osteoblastic differentiation. J. Bone Min. Metab. 27, 158-167 (2009).
61. Wong, S. Y., Reiter, J. F. The primary cilium: at the crossroads of mammalian hedgehog signalling. Curr. Top. Dev. Biol. 85, 225-260 (2008).
62. Bijlsma, M. F., Damhofer, H., Roelink, H. Hedgehog-stimulated chemotaxis is mediated by smoothened located outside the primary cilium. Sci. Signal. 5, 60 (2012).
63. Farley, F. W., Soriano, P., Steffen, L. S., Dymecki, S. M. Widespread recombinase expression using FLPeR (flipper) mice. Genesis 28, 106-110 (2000).
64. He, X. et al. BMP2 genetically engineered MSCs and EPCs promote vascularized bone regeneration in rat critical-sized calvarial bone defects. PLoS ONE 8, e60473 (2013).
65. Kurita, S. et al. GLI3-dependent repression of DR4 mediates hedgehog antagonism of TRAIL-induced apoptosis. Oncogene 29, 4848-4858 (2010).
66. Vallenius, T. et al. An association between NUAK2 and MRIP reveals a novel mechanism for regulation of actin stress fibres. J. Cell Sci. 124, 384-393 (2011).
67. Wei, S., Gao, X., Du, J., Su, J., Xu, Z. Angiogenin enhances cell migration by regulating stress fibre assembly and focal adhesion dynamics. PLoS ONE 6, e28797 (2011).
68. Ovchinnikov, D. Alcian blue/alizarin red staining of cartilage and bone in mouse. Cold Spring Harb. Protoc. 2009, pdb prot5170 (2009).
69. Yuan, X. et al. Regulators of G protein signalling 12 promotes osteoclastogenesis in bone remodelling and pathological bone loss. Cell Death Diff. 22, 2046-2057 (2015).
70. Livak, K. J., Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402-408 (2001).