Systemic Inhibition of Canonical Notch Signaling Results in Sustained Callus Inflammation and Alters Multiple Phases of Fracture Healing

PLoS ONE

Volumn 8, Issue 7, 2013, Pages

  Dishowitz, Michael I ^a   Mutyaba, Patricia L ^b   Takacs, Joel D ^b   Barr, Andrew M ^a   Engiles, Julie B ^c   Ahn, Jaimo ^d   Hankenson, Kurt D ^b,d  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CRE RECOMBINASE; CYCLINE; NOTCH RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CALLUS; CARTILAGE MATRIX; CELL DENSITY; CELL DIFFERENTIATION; CHONDROGENESIS; CONTROLLED STUDY; DISEASE SEVERITY; EMBRYO; ENZYME INHIBITION; FEMALE; FRACTURE HEALING; GENE SEQUENCE; GENETIC TRANSCRIPTION; MALE; MORPHOMETRICS; MOUSE; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOCYTE; OSTEOLYSIS; PROMOTER REGION; PROTEIN ANALYSIS; PROTEIN FUNCTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

ANIMALS; BONE REMODELING; BONY CALLUS; CARTILAGE; CELL DIFFERENTIATION; CHONDROGENESIS; FEMALE; FRACTURE HEALING; GENE EXPRESSION; INFLAMMATION; MALE; MESENCHYMAL STROMAL CELLS; MICE; NUCLEAR PROTEINS; OSTEOBLASTS; OSTEOGENESIS; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION;

MUS; MUS MUSCULUS;

EID: 84879772616     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0068726     Document Type: Article

References (46)

1. Einhorn TA, (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res: pp. S7-21. PubMed: 9917622.
2. Audigé L, Griffin D, Bhandari M, Kellam J, Rüedi TP, (2005) Path analysis of factors for delayed healing and nonunion in 416 operatively treated tibial shaft fractures. Clin Orthop Relat Res 438: 221-232. PubMed: 16131895.
3. Braithwaite RS, Col NF, Wong JB, (2003) Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc 51: 364-370. doi:10.1046/j.1532-5415.2003.51110.x. PubMed: 12588580.
4. Dimitriou R, Jones E, McGonagle D, Giannoudis PV, (2011) Bone regeneration: current concepts and future directions. BMC Med 9: 66. doi:10.1186/1741-7015-9-66. PubMed: 21627784.
5. Carragee EJ, Hurwitz EL, Weiner BK, Bono CM, Rothman DJ, (2011) Future directions for The spine journal: managing and reporting conflict of interest issues. Spine J 11: 695-697. doi:10.1016/j.spinee.2011.08.418. PubMed: 21925411.
6. Artavanis-Tsakonas S, Rand MD, Lake RJ, (1999) Notch signaling: cell fate control and signal integration in development. Science 284: 770-776. doi:10.1126/science.284.5415.770. PubMed: 10221902.
7. Hilton MJ, Tu X, Wu X, Bai S, Zhao H, et al. (2008) Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med 14: 306-314. doi:10.1038/nm1716. PubMed: 18297083.
8. Dong Y, Jesse AM, Kohn A, Gunnell LM, Honjo T, et al. (2010) RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development. Development 137: 1461-1471. doi:10.1242/dev.042911. PubMed: 20335360.
9. Kohn A, Dong Y, Mirando AJ, Jesse AM, Honjo T, et al. (2012) Cartilage-specific RBPjkappa-dependent and-independent Notch signals regulate cartilage and bone development. Development 139: 1198-1212. doi:10.1242/dev.070649. PubMed: 22354840.
10. Mead TJ, Yutzey KE, (2009) Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development. Proc Natl Acad Sci U S A 106: 14420-14425. doi:10.1073/pnas.0902306106. PubMed: 19590010.
11. Dishowitz MI, Terkhorn SP, Bostic SA, Hankenson KD, (2012) Notch signaling components are upregulated during both endochondral and intramembranous bone regeneration. J Orthop Res 30: 296-303. doi:10.1002/jor.21518. PubMed: 21818769.
12. Oldershaw RA, Tew SR, Russell AM, Meade K, Hawkins R, et al. (2008) Notch signaling through Jagged-1 is necessary to initiate chondrogenesis in human bone marrow stromal cells but must be switched off to complete chondrogenesis. Stem Cells 26: 666-674. doi:10.1634/stemcells.2007-0806. PubMed: 18192230.
13. Engin F, Yao Z, Yang T, Zhou G, Bertin T, et al. (2008) Dimorphic effects of Notch signaling in bone homeostasis. Nat Med 14: 299-305. doi:10.1038/nm1712. PubMed: 18297084.
14. Zanotti S, Smerdel-Ramoya A, Stadmeyer L, Durant D, Radtke F, et al. (2008) Notch inhibits osteoblast differentiation and causes osteopenia. Endocrinology 149: 3890-3899. doi:10.1210/en.2008-0140. PubMed: 18420737.
15. Canalis E, Parker K, Feng JQ, Zanotti S, (2013) Osteoblast lineage-specific effects of notch activation in the skeleton. Endocrinology 154: 623-634.
16. Bai S, Kopan R, Zou W, Hilton MJ, Ong CT, et al. (2008) NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem 283: 6509-6518. doi:10.1074/jbc.M707000200. PubMed: 18156632.
17. Vortkamp A, Pathi S, Peretti GM, Caruso EM, Zaleske DJ, et al. (1998) Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair. Mech Dev 71: 65-76. doi:10.1016/S0925-4773(97)00203-7. PubMed: 9507067.
18. Ferguson C, Alpern E, Miclau T, Helms JA, (1999) Does adult fracture repair recapitulate embryonic skeletal formation? Mech Dev 87: 57-66. doi:10.1016/S0925-4773(99)00142-2. PubMed: 10495271.
19. Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA, (2003) Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 88: 873-884. doi:10.1002/jcb.10435. PubMed: 12616527.
20. Chigurupati S, Arumugam TV, Son TG, Lathia JD, Jameel S, et al. (2007) Involvement of notch signaling in wound healing. PLOS ONE 2: e1167. doi:10.1371/journal.pone.0001167. PubMed: 18000539.
21. Weng AP, Nam Y, Wolfe MS, Pear WS, Griffin JD, et al. (2003) Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol 23: 655-664. doi:10.1128/MCB.23.2.655-664.2003. PubMed: 12509463.
22. Maillard I, Weng AP, Carpenter AC, Rodriguez CG, Sai H, et al. (2004) Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood 104: 1696-1702. doi:10.1182/blood-2004-02-0514. PubMed: 15187027.
23. Tu L, Fang TC, Artis D, Shestova O, Pross SE, et al. (2005) Notch signaling is an important regulator of type 2 immunity. J Exp Med 202: 1037-1042. doi:10.1084/jem.20050923. PubMed: 16230473.
24. Maillard I, Tu L, Sambandam A, Yashiro-Ohtani Y, Millholland J, et al. (2006) The requirement for Notch signaling at the beta-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. J Exp Med 203: 2239-2245. doi:10.1084/jem.20061020. PubMed: 16966428.
25. Maillard I, Koch U, Dumortier A, Shestova O, Xu L, et al. (2008) Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. Cell Stem Cell 2: 356-366. doi:10.1016/j.stem.2008.02.011. PubMed: 18397755.
26. Kühn R, Schwenk F, Aguet M, Rajewsky K, (1995) Inducible gene targeting in mice. Science 269: 1427-1429. doi:10.1126/science.7660125. PubMed: 7660125.
27. Glatt V, Canalis E, Stadmeyer L, Bouxsein ML, (2007) Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res 22: 1197-1207.
28. Buie HR, Moore CP, Boyd SK, (2008) Postpubertal architectural developmental patterns differ between the L3 vertebra and proximal tibia in three inbred strains of mice. J Bone Miner Res 23: 2048-2059. doi:10.1359/jbmr.080808. PubMed: 18684086.
29. Shitaye H, Hankenson KD, (2010) Postnatal Expression of the Notch Inhibitor Dominant-Negative Mastermind-like 1 Decreases Trabecular Bone Mass. Transcripts of the Orthopaedic Research Society.
30. Bonnarens F, Einhorn TA, (1984) Production of a standard closed fracture in laboratory animal bone. J Orthop Res 2: 97-101. doi:10.1002/jor.1100020115. PubMed: 6491805.
31. Taylor DK, Meganck JA, Terkhorn S, Rajani R, Naik A, et al. (2009) Thrombospondin-2 influences the proportion of cartilage and bone during fracture healing. J Bone Miner Res 24: 1043-1054. doi:10.1359/jbmr.090101. PubMed: 19123916.
32. Tao J, Chen S, Yang T, Dawson B, Munivez E, et al. (2010) Osteosclerosis owing to Notch gain of function is solely Rbpj-dependent. J Bone Miner Res 25: 2175-2183. doi:10.1002/jbmr.115. PubMed: 20499347.
33. Salie R, Kneissel M, Vukevic M, Zamurovic N, Kramer I, et al. (2010) Ubiquitous overexpression of Hey1 transcription factor leads to osteopenia and chondrocyte hypertrophy in bone. Bone 46: 680-694. doi:10.1016/j.bone.2009.10.022. PubMed: 19857617.
34. Hankenson KD, Bain SD, Kyriakides TR, Smith EA, Goldstein SA, et al. (2000) Increased marrow-derived osteoprogenitor cells and endosteal bone formation in mice lacking thrombospondin 2. J Bone Miner Res 15: 851-862. PubMed: 10804014.
35. Gerstenfeld LC, Wronski TJ, Hollinger JO, Einhorn TA, (2005) Application of histomorphometric methods to the study of bone repair. J Bone Miner Res 20: 1715-1722. doi:10.1359/JBMR.050702. PubMed: 16160729.
36. Mountziaris PM, Spicer PP, Kasper FK, Mikos AG, (2011) Harnessing and modulating inflammation in strategies for bone regeneration. Tissue Eng B Rev 17: 393-402. doi:10.1089/ten.teb.2011.0182. PubMed: 21615330.
37. Alblowi J, Kayal RA, Siqueira M, McKenzie E, Krothapalli N, et al. (2009) High levels of tumor necrosis factor-alpha contribute to accelerated loss of cartilage in diabetic fracture healing. Am J Pathol 175: 1574-1585. doi:10.2353/ajpath.2009.090148. PubMed: 19745063.
38. Bastian O, Pillay J, Alblas J, Leenen L, Koenderman L, et al. (2011) Systemic inflammation and fracture healing. J Leukoc Biol 89: 669-673. doi:10.1189/jlb.0810446. PubMed: 21208896.
39. Ostroukhova M, Qi Z, Oriss TB, Dixon-McCarthy B, Ray P, et al. (2006) Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane-bound TGF-beta. J Clin Invest 116: 996-1004. doi:10.1172/JCI26490. PubMed: 16543950.
40. Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, et al. (1991) Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 10: 4025-4031. PubMed: 1721867.
41. Niki Y, Yamada H, Seki S, Kikuchi T, Takaishi H, et al. (2001) Macrophage- and neutrophil-dominant arthritis in human IL-1 alpha transgenic mice. J Clin Invest 107: 1127-1135. doi:10.1172/JCI11530. PubMed: 11342576.
42. Lubberts E, Joosten LA, Oppers B, van den Bersselaar L, Coenen-de Roo CJ, et al. (2001) IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol 167: 1004-1013. PubMed: 11441109.
43. Caparbo VF, Prada F, Silva CA, Regio PL, Pereira RM, (2009) Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts "in vitro". Clin Rheumatol 28: 71-77. doi:10.1007/s10067-008-0985-y. PubMed: 18685881.
44. Cappellen D, Luong-Nguyen NH, Bongiovanni S, Grenet O, Wanke C, et al. (2002) Transcriptional program of mouse osteoclast differentiation governed by the macrophage colony-stimulating factor and the ligand for the receptor activator of NFkappa B. J Biol Chem 277: 21971-21982. doi:10.1074/jbc.M200434200. PubMed: 11923298.
45. Cardoso L, Herman BC, Verborgt O, Laudier D, Majeska RJ, et al. (2009) Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue. J Bone Miner Res 24: 597-605. doi:10.1359/jbmr.081210. PubMed: 19049324.
46. Emerton KB, Hu B, Woo AA, Sinofsky A, Hernandez C, et al. (2010) Osteocyte apoptosis and control of bone resorption following ovariectomy in mice. Bone 46: 577-583. doi:10.1016/j.bone.2009.11.006. PubMed: 19925896.