Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits

Journal of Bone and Mineral Research

Volumn 30, Issue 11, 2015, Pages 2044-2057

  Zheng, Li Zhen ^a   Cao, Hui Juan ^b   Chen, Shi Hui ^a   Tang, Tao ^a   Fu, Wei Min ^a,c   Huang, Le ^a   Chow, Dick Ho Kiu ^a   Wang, Yi Xiang ^a   Griffith, James Francis ^a   He, Wei ^d   Zhou, Hong ^e   Zhao, De Wei ^c   Zhang, Ge ^a,f   Wang, Xin Luan ^a,b   Qin, Ling ^a,b  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b SHENZHEN INSTITUTES OF ADVANCED TECHNOLOGY   (China)

^c DALIAN UNIVERSITY   (China)

^d GUANGZHOU UNIVERSITY OF CHINESE MEDICINE   (China)

^e UNIVERSITY OF SYDNEY   (Australia)

^f HONG KONG BAPTIST UNIVERSITY   (Hong Kong)

Author keywords

OSTEONECROSIS; REPAIR; SIRNA; SRC

Indexed keywords

GADOTERIC ACID; PROTEIN; PROTEIN SRC; SMALL INTERFERING RNA; SODIUM CHLORIDE; UNCLASSIFIED DRUG; VASCULOTROPIN; PROTEIN TYROSINE KINASE; STEROID;

ANGIOGRAPHY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD VESSEL PERMEABILITY; BONE DENSITY; BONE MARROW; BONE MARROW EDEMA; BONE NECROSIS; BONE TISSUE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; CONTROLLED STUDY; FINITE ELEMENT ANALYSIS; GENE SILENCING; HISTOLOGY; MALE; MICRO-COMPUTED TOMOGRAPHY; MORPHOMETRICS; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OSTEOLYSIS; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; STEROID ASSOCIATED OSTEONECROSIS; TRABECULAR BONE; VASCULARIZATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; BONE DEVELOPMENT; CHEMICALLY INDUCED; DISEASE MODEL; ENZYMOLOGY; METABOLISM; PATHOLOGY; PERFUSION; RABBIT; RADIOGRAPHY; WOUND HEALING;

ANIMALS; DISEASE MODELS, ANIMAL; FINITE ELEMENT ANALYSIS; GENE KNOCKDOWN TECHNIQUES; GENE SILENCING; MALE; MODELS, BIOLOGICAL; OSTEOGENESIS; OSTEONECROSIS; PERFUSION; RABBITS; RNA, SMALL INTERFERING; SRC-FAMILY KINASES; STEROIDS; WOUND HEALING; X-RAY MICROTOMOGRAPHY;

EID: 84945438370     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2542     Document Type: Article

References (65)

1. Mok CC, Lau CS, Wong RW., Risk factors for avascular bone necrosis in systemic lupus erythematosus. Br J Rheumatol. 1998; 37 (8): 895-900.
2. So LK, Lau AC, Yam LY, et al., Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet. 2003; 361 (9369): 1615-7.
3. Xie X-H, Wang X-L, Yang H-L, Zhao D-W, Qin L., Steroid-associated osteonecrosis: epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview). J Orthop Translat. 2015; 3 (2): 58-70.
4. Hernigou P, Poignard A, Zilber S, Rouard H., Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop. 2009; 43 (1): 40-5.
5. Rahman WA, Garbuz DS, Masri BA., Total hip arthroplasty in steroid-induced osteonecrosis: early functional and radiological outcomes. Can J Surg. 2013; 56 (1): 41-6.
6. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME., Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum. 2002; 32 (2): 94-124.
7. Chan MH, Chan PK, Griffith JF, et al., Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy. Pathology. 2006; 38 (3): 229-35.
8. Law RK, Lee EW, Poon PY, Lau TC, Kwok KM, Chan AC., The functional capacity of healthcare workers with history of severe acute respiratory distress syndrome (SARS) complicated with avascular necrosis-case report. Work. 2008; 30 (1): 17-26.
9. Lieberman JR, Berry DJ, Mont MA, et al., Osteonecrosis of the hip: management in the 21st century. Instr Course Lect. 2003; 52: 337-55.
10. Mont MA, Jones LC, Hungerford DS., Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006; 88 (5): 1117-32.
11. ARCO-Committee on Terminology and Staging; Gardeniers JWM, chairman. The ARCO perspective for reaching one uniform staging system of osteonecrosis. In:, Schoutens A, Arlet J, Gardeniers JWM, Hughes SPF, editors. Bone circulation and vascularization in normal and pathological conditions. New York: Plenum Press; 1993. p. 375-80.
12. Mont MA, Jones LC, Einhorn TA, Hungerford DS, Reddi AH., Osteonecrosis of the femoral head. Potential treatment with growth and differentiation factors. Clin Orthop Relat Res. 1998 (355 Suppl): S314-35.
13. Masaki I, Yonemitsu Y, Yamashita A, et al., Angiogenic gene therapy for experimental critical limb ischemia: acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2. Circ Res. 2002; 90 (9): 966-73.
14. Hershey JC, Baskin EP, Corcoran HA, et al., Vascular endothelial growth factor stimulates angiogenesis without improving collateral blood flow following hindlimb ischemia in rabbits. Heart Vessels. 2003; 18 (3): 142-9.
15. Agarwala S, Shah S, Joshi VR., The use of alendronate in the treatment of avascular necrosis of the femoral head: follow-up to eight years. J Bone Joint Surg Br. 2009; 91 (8): 1013-8.
16. Griffith JF, Antonio GE, Kumta SM, et al., Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids. Radiology. 2005; 235 (1): 168-75.
17. Maes C, Kobayashi T, Selig MK, et al., Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010; 19 (2): 329-44.
18. Senger DR, Perruzzi CA, Feder J, Dvorak HF., A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res. 1986; 46 (11): 5629-32.
19. van Bruggen N, Thibodeaux H, Palmer JT, et al., VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest. 1999; 104 (11): 1613-20.
20. Weis S, Shintani S, Weber A, et al., Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction. J Clin Invest. 2004; 113 (6): 885-94.
21. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA., Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004; 56 (4): 549-80.
22. Vadasz Z, Misselevich I, Norman D, Peled E, Boss JH., Localization of vascular endothelial growth factor during the early reparative phase of the rats' vessels deprivation-induced osteonecrosis of the femoral heads. Exp Mol Pathol. 2004; 77 (2): 145-8.
23. Kim HK, Bian H, Randall T, Garces A, Gerstenfeld LC, Einhorn TA., Increased VEGF expression in the epiphyseal cartilage after ischemic necrosis of the capital femoral epiphysis. J Bone Miner Res. 2004; 19 (12): 2041-8.
24. Yeatman TJ., A renaissance for SRC. Nat Rev Cancer. 2004; 4 (6): 470-80.
25. Rucci N, Susa M, Teti A., Inhibition of protein kinase c-Src as a therapeutic approach for cancer and bone metastases. Anticancer Agents Med Chem. 2008; 8 (3): 342-9.
26. Eliceiri BP, Paul R, Schwartzberg PL, Hood JD, Leng J, Cheresh DA., Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell. 1999; 4 (6): 915-24.
27. Boyce BF, Yoneda T, Lowe C, Soriano P, Mundy GR., Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J Clin Invest. 1992; 90 (4): 1622-7.
28. Soriano P, Montgomery C, Geske R, Bradley A., Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991; 64 (4): 693-702.
29. Schwartzberg PL, Xing L, Hoffmann O, et al., Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src-/- mutant mice. Genes Dev. 1997; 11 (21): 2835-44.
30. Zhang G, Sheng H, He YX, et al., Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid-associated osteonecrotic lesions. Arthritis Rheum. 2009; 60 (10): 2966-77.
31. Zhang G, He YX, Xie XH, et al., Activated Src phosphorylation accompanied by both vascular hyperpermeability and dominant bone resorption during destructive repair of steroid-associated osteonecrotic lesions in rabbits. Bone. 2010; 47 Suppl 3: S401.
32. Cao HJ, Zheng LZ, Wang N, et al., Src blockage by siRNA inhibits VEGF-induced vascular hyperpemeability and osteoclast activity-an in vitro mechanism study for preventing destructive repair of osteonecrosis. Bone. 2015 May; 74: 58-68.
33. Zhang G, Guo B, Wu H, et al., A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat Med. 2012; 18 (2): 307-14.
34. Qin L, Zhang G, Sheng H, et al., Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone. Bone. 2006; 39 (4): 863-71.
35. Tang T, Zhang G, Guo BS, Hung LK, Qin L., A rabbit specific Src siRNA with high knockdown efficiency in vitro. Bone. 2010; 47: S425-S6.
36. Brunt KR, Hall SR, Ward CA, Melo LG., Endothelial progenitor cell and mesenchymal stem cell isolation, characterization, viral transduction. Methods Mol Med. 2007; 139: 197-210.
37. Chen WT, Shih TT, Chen RC, et al., Blood perfusion of vertebral lesions evaluated with gadolinium-enhanced dynamic MRI: in comparison with compression fracture and metastasis. J Magn Reson Imaging. 2002; 15 (3): 308-14.
38. Wang YX, Griffith JF, Deng M, et al., Compromised perfusion in femoral head in normal rats: distinctive perfusion MRI evidence of contrast washout delay. Br J Radiol. 2012; 85 (1016): e436-41.
39. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R., Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010; 25 (7): 1468-86.
40. Xie XH, Wang XL, Zhang G, et al., Impaired bone healing in rabbits with steroid-induced osteonecrosis. J Bone Joint Surg. 2010; 93 (4): 558-65.
41. Zhang G, Qin L, Sheng H, et al., Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition. Bone. 2007; 40 (3): 685-92.
42. Duvall CL, Taylor WR, Weiss D, Guldberg RE., Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury. Am J Physiol Heart Circ Physiol. 2004; 287 (1): H302-10.
43. Yamamoto T, Irisa T, Sugioka Y, Sueishi K., Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits. Arthritis Rheum. 1997; 40 (11): 2055-64.
44. Dempster DW, Compston JE, Drezner MK, et al., Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 2013; 28 (1): 2-17.
45. Allred DC, Clark GM, Elledge R, et al., Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst. 1993; 85 (3): 200-6.
46. Maitra A, Ashfaq R, Gunn CR, et al., Cyclooxygenase 2 expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging. Am J Clin Pathol. 2002; 118 (2): 194-201.
47. Ito H, Matsuno T, Minami A., Relationship between bone marrow edema and development of symptoms in patients with osteonecrosis of the femoral head. AJR Am J Roentgenol. 2006; 186 (6): 1761-70.
48. Nishii T, Sugano N, Ohzono K, Sakai T, Haraguchi K, Yoshikawa H., Progression and cessation of collapse in osteonecrosis of the femoral head. Clin Orthop Relat Res. 2002 (400): 149-57.
49. Sun Y, Feng Y, Zhang C., The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. Joint Bone Spine. 2009; 76 (6): 685-90.
50. Hernigou P, Beaujean F, Lambotte JC., Decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid-induced osteonecrosis. J Bone Joint Surg. 1999; 81 (2): 349-55.
51. Xie XH, Wang XL, He YX, et al., Promotion of bone repair by implantation of cryopreserved bone marrow-derived mononuclear cells in a rabbit model of steroid-associated osteonecrosis. Arthritis Rheum. 2012; 64 (5): 1562-71.
52. Nagai T, Sato M, Kutsuna T, et al., Intravenous administration of anti-vascular endothelial growth factor humanized monoclonal antibody bevacizumab improves articular cartilage repair. Arthritis Res Ther. 2010; 12 (5): R178.
53. Atsumi T, Kuroki Y., Role of impairment of blood supply of the femoral head in the pathogenesis of idiopathic osteonecrosis. Clin Orthop Relat Res. 1992 (277): 22-30.
54. Liu Y, Berendsen AD, Jia S, et al., Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation. J Clin Invest. 2012; 122 (9): 3101-13.
55. Sun Y, Ma YC, Huang J, Chen KY, McGarrigle DK, Huang XY., Requirement of SRC-family tyrosine kinases in fat accumulation. Biochemistry. 2005; 44 (44): 14455-62.
56. Marzia M, Sims NA, Voit S, et al., Decreased c-Src expression enhances osteoblast differentiation and bone formation. J Cell Biol. 2000; 151 (2): 311-20.
57. Henriksen K, Karsdal M, Delaisse JM, Engsig MT., RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through an ERK1/2-dependent mechanism. J Biol Chem. 2003; 278 (49): 48745-53.
58. Sipola A, Nelo K, Hautala T, Ilvesaro J, Tuukkanen J., Endostatin inhibits VEGF-A induced osteoclastic bone resorption in vitro. BMC Musculoskelet Disord. 2006; 7: 56.
59. Yang Q, McHugh KP, Patntirapong S, Gu X, Wunderlich L, Hauschka PV., VEGF enhancement of osteoclast survival and bone resorption involves VEGF receptor-2 signaling and beta3-integrin. Matrix Biol. 2008; 27 (7): 589-99.
60. Neff L, Amling M, Baron R., c-Src deletion alters adhesion structures in the osteoclast: redistribution of podosomes and formation of focal adhesions. J Bone Miner Res. 1996; 11: S290. Abstract M436.
61. Zheng LZ, Liu Z, Lei M, et al., Steroid-associated hip joint collapse in bipedal emus. PLoS One. 2013; 8 (10): e76797.
62. Cui Q, Wang GJ, Su CC, Balian G., The Otto Aufranc Award. Lovastatin prevents steroid induced adipogenesis and osteonecrosis. Clin Orthop Relat Res. 1997 Nov;(344): 8-19.
63. Cui L, Cohen JL, Chu CK, Wich PR, Kierstead PH, Fréchet JM., Conjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNA. J Am Chem Soc. 2012; 134 (38): 15840-8.
64. Jackson AL, Bartz SR, Schelter J, et al., Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol. 2003; 21 (6): 635-7.
65. Jackson AL, Burchard J, Leake D, et al., Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA. 2006; 12 (7): 1197-205.