Adipogenic differentiation of hMSCs is mediated by recruitment of IGF-1r onto the primary cilium associated with cilia elongation

Stem Cells

Volumn 33, Issue 6, 2015, Pages 1952-1961

  Dalbay, Melis T ^a   Thorpe, Stephen D ^a   Connelly, John T ^b   Chapple, J Paul ^b   Knight, Martin M ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Adipogenic differentiation; Chondrogenic differentiation; Cilia; Human mesenchymal stem cell; IGF 1 receptor; Osteogenic differentiation

Indexed keywords

ALKALINE PHOSPHATASE; ALPHA TUBULIN; COLLAGEN TYPE 2; DEXAMETHASONE; F ACTIN; FAT DROPLET; INDOMETACIN; INSULIN; INSULIN LIKE GROWTH FACTOR 1 RECEPTOR BETA; INSULIN RECEPTOR; ISOBUTYLMETHYLXANTHINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; SMALL INTERFERING RNA; SOMATOMEDIN C RECEPTOR; UNCLASSIFIED DRUG;

ADIPOGENESIS; ADIPOGENIC DIFFERENTIATION; ARTICLE; BONE MARROW DERIVED MESENCHYMAL STEM CELL; CELL CULTURE; CELL DIFFERENTIATION; CELL ELONGATION; CELL LABELING; CELL LINEAGE; CHONDROGENESIS; CILIA ELONGATION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; EUKARYOTIC FLAGELLUM; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HYPOTHESIS; IMMUNOCYTOCHEMISTRY; LIPID STORAGE; NEGATIVE FEEDBACK; PREVALENCE; PRIMARY CELL; REGULATORY MECHANISM; WESTERN BLOTTING; ADIPOCYTE; CELL CYCLE; CYTOLOGY; MESENCHYMAL STROMA CELL; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ADIPOCYTES; ADIPOGENESIS; CELL CYCLE; CELLS, CULTURED; CILIA; HUMANS; MESENCHYMAL STROMAL CELLS; RECEPTOR, IGF TYPE 1; SIGNAL TRANSDUCTION;

EID: 84929773975     PISSN: 10665099     EISSN: 15494918     Source Type: Journal    
DOI: 10.1002/stem.1975     Document Type: Article

References (42)

1. Satir P, Pedersen LB, Christensen ST,. The primary cilium at a glance. J Cell Sci 2010; 123: 499-503.
2. Goetz SC, Anderson KV,. The primary cilium: A signalling centre during vertebrate development. Nat Rev Genet 2010; 11: 331-344.
3. Veland IR, Awan A, Pedersen LB, et al., Primary cilia and signaling pathways in mammalian development, health and disease. Nephron Physiol 2009; 111: p39-53.
4. Wallingford JB, Mitchell B,. Strange as it may seem: The many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev 2011; 25: 201-213.
5. Rohatgi R, Milenkovic L, Scott MP,. Patched1 regulates hedgehog signaling at the primary cilium. Science 2007; 317: 372-376.
6. Corbit KC, Aanstad P, Singla V, et al., Vertebrate Smoothened functions at the primary cilium. Nature 2005; 437: 1018-1021.
7. Ezratty EJ, Stokes N, Chai S, et al., A role for the primary cilium in Notch signaling and epidermal differentiation during skin development. Cell 2011; 145: 1129-1141.
8. Hoey DA, Tormey S, Ramcharan S, et al., Primary cilia-mediated mechanotransduction in human mesenchymal stem cells. Stem Cells 2012; 30: 2561-2570.
9. Clement CA, Ajbro KD, Koefoed K, et al., TGF-beta signaling is associated with endocytosis at the pocket region of the primary cilium. Cell Rep 2013; 3: 1806-1814.
10. Pedersen LB, Rosenbaum JL,. Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling. Curr Top Dev Biol 2008; 85: 23-61.
11. Marshall WF, Qin H, Rodrigo Brenni M, et al., Flagellar length control system: Testing a simple model based on intraflagellar transport and turnover. Mol Biol Cell 2005; 16: 270-278.
12. Berbari NF, O'Connor AK, Haycraft CJ, et al., The primary cilium as a complex signaling center. Curr Biol 2009; 19: R526-R535.
13. Hildebrandt F, Benzing T, Katsanis N,. Ciliopathies. N Engl J Med 2011; 364: 1533-1543.
14. Bodle JC, Rubenstein CD, Phillips ME, et al., Primary cilia: The chemical antenna regulating human adipose-derived stem cell osteogenesis. PLoS One 2013; 8: e62554.
15. Plaisant M, Fontaine C, Cousin W, et al., Activation of hedgehog signaling inhibits osteoblast differentiation of human mesenchymal stem cells. Stem Cells 2009; 27: 703-713.
16. Qiu N, Cao L, David V, et al., Kif3a deficiency reverses the skeletal abnormalities in Pkd1 deficient mice by restoring the balance between osteogenesis and adipogenesis. PLoS One 2010; 5: e15240.
17. Tummala P, Arnsdorf EJ, Jacobs CR,. The role of primary cilia in mesenchymal stem cell differentiation: A pivotal switch in guiding lineage commitment. Cell Mol Bioeng 2010; 3: 207-212.
18. Yang S, Wang C,. The intraflagellar transport protein IFT80 is required for cilia formation and osteogenesis. Bone 2012; 51: 407-417.
19. Marion V, Mockel A, De Melo C, et al., BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response. Cell Metab 2012; 16: 363-377.
20. Wang C, Yuan X, Yang S,. IFT80 is essential for chondrocyte differentiation by regulating Hedgehog and Wnt signaling pathways. Exp Cell Res 2013; 319: 623-632.
21. Huang JG, Shen CB, Wu WB, et al., Primary cilia mediate sonic hedgehog signaling to regulate neuronal-like differentiation of bone mesenchymal stem cells for resveratrol induction in vitro. J Neurosci Res 2014; 92: 587-596.
22. McMurray RJ, Wann AK, Thompson CL, et al., Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells. Sci Rep 2013; 3: 3545.
23. He M, Subramanian R, Bangs F, et al., The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment. Nat Cell Biol 2014; 16: 663-672.
24. McGlashan SR, Knight MM, Chowdhury TT, et al., Mechanical loading modulates chondrocyte primary cilia incidence and length. Cell Biol Int 2010; 34: 441-446.
25. Besschetnova TY, Kolpakova-Hart E, Guan Y, et al., Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol 2010; 20: 182-187.
26. Ludington WB, Wemmer KA, Lechtreck KF, et al., Avalanche-like behavior in ciliary import. Proc Natl Acad Sci U S A 2013; 110: 3925-3930.
27. Thompson CL, Chapple JP, Knight MM,. Primary cilia disassembly down-regulates mechanosensitive hedgehog signalling: A feedback mechanism controlling ADAMTS-5 expression in chondrocytes. Osteoarthritis Cartilage 2014; 22: 490-498.
28. Brown JA, Santra T, Owens P, et al., Primary cilium-associated genes mediate bone marrow stromal cell response to hypoxia. Stem Cell Res 2014; 13: 284-299.
29. Quarmby LM, Parker JD,. Cilia and the cell cycle? J Cell Biol 2005; 169: 707-710.
30. Spiegelman BM, Ginty CA,. Fibronectin modulation of cell shape and lipogenic gene expression in 3T3-adipocytes. Cell 1983; 35: 657-666.
31. Rodriguez Fernandez JL, Ben-Ze'ev A,. Regulation of fibronectin, integrin and cytoskeleton expression in differentiating adipocytes: Inhibition by extracellular matrix and polylysine. Differentiation 1989; 42: 65-74.
32. Zhu D, Shi S, Wang H, et al., Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3T3-L1 preadipocytes. J Cell Sci 2009; 122: 2760-2768.
33. Serrero G, Lepak N,. Insulin but not ICF-I is required for the maintenance of the adipose phenotype in the adipogenic cell line 1246. In Vitro Cell Dev Biol 1999; 35: 642-646.
34. Smith PJ, Wise LS, Berkowitz R, et al., Insulin-like growth factor-I is an essential regulator of the differentiation of 3t3-L1 adipocytes. J Biol Chem 1988; 263: 9402-9408.
35. Pitaval A, Tseng Q, Bornens M, et al., Cell shape and contractility regulate ciliogenesis in cell cycle-arrested cells. J Cell Biol 2010; 191: 303-312.
36. Kersten S, Desvergne B, Wahli W,. Roles of PPARs in health and disease. Nature 2000; 405: 421-424.
37. Berger J, Patel HV, Woods J, et al., A PPARgamma mutant serves as a dominant negative inhibitor of PPAR signaling and is localized in the nucleus. Mol Cell Endocrinol 2000; 162: 57-67.
38. Pittenger MF, Mackay AM, Beck SC, et al., Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147.
39. Scavo LM, Karas M, Murray M, et al., Insulin-like growth factor-I stimulates both cell growth and lipogenesis during differentiation of human mesenchymal stem cells into adipocytes. J Clin Endocrinol Metabol 2004; 89: 3543-3553.
40. Marion V, Stoetzel C, Schlicht D, et al., Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proc Natl Acad Sci U S A 2009; 106: 1820-1825.
41. Alieva IB, Vorobjev IA,. Vertebrate primary cilia: A sensory part of centrosomal complex in tissue cells, but a "sleeping beauty" in cultured cells? Cell Biol Int 2004; 28: 139-150.
42. Davenport JR, Watts AJ, Roper VC, et al., Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr Biol 2007; 17: 1586-1594.