RESEARCH PROGRESS OF HEME OXYGENASE 1 IN BONE TISSUE ENGINEERING_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Xiaopeng ^1,2 , HU Yongcheng ² , FANG Cheng ^1,2 , ZHANG Rongxin ¹ , WANG Han ^1,2 , HE Xin ^1,2 , YUAN Binbin ^1,2

1Graduate Department of Tianjin Medical University, Tianjin, 300070, P.R.China;;
2Department of Bone and Soft Tissue Tumor, Tianjin Hospital. Corresponding author: HU Yongcheng, E-mail: yongchenghu@126.com;;
ZHANG Rongxin, E-mail: rongxinz@yahoo.com;

Corresponding author：

Keywords：

Heme oxygenase 1; Growth factor; Bone tissue engineering

DOI：

10.7507/1002-1892.20130274

Video：

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Objective To review the latest research progress of heme oxygenase 1 (HO-1), to thoroughly understand different functions of HO-1 and its influence on osteogenesis and angiogenesis of stem cells, and to analyze HO-1 application in bone tissue engineering. Methods Domestic and international literature on HO-1 in recent years was extensively reviewed and analyzed. Results The activity of HO-1 and its enzymatic products not only have the properties of anti-inflammatory, anti-apoptosis, and cytoprotection, but also can promote angiogenesis combined with other growth factors and protect the vessel which already exist. Moreover, HO-1 has an effect on the proliferation, paracrine signaling, osteoblastic differentiation, and anti-apoptosis of stem cells. Conclusion HO-1 can be used as a multi-function growth factor in bone tissue engineering, but more investigation should emphasis on synergistic effect of each function so as to improve bone repair.

Citation： CHEN Xiaopeng,HU Yongcheng,FANG Cheng,ZHANG Rongxin,WANG Han,HE Xin,YUAN Binbin. RESEARCH PROGRESS OF HEME OXYGENASE 1 IN BONE TISSUE ENGINEERING. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(10): 1256-1261. doi: 10.7507/1002-1892.20130274 Copy

1.	Evans CH. Gene delivery to bone. Advanced Drug Delivery Reviews, 2012, 64(12): 1331-1340.
2.	刘显挺, 江潞, 曾昕, 等. 调控VEGF的转录因子及其与肿瘤的关系. 中国肿瘤生物治疗杂志, 2010, 17(4): 468-472.
3.	Kim YM, Pae HO, Park JE, et al. Heme oxygenase in the regulation of vascular biology: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal, 2011, 14(1): 137-167.
4.	Zarjou A, Kim J, Traylor AM, et al. Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1. Am J Physiol Renal Physiol, 2011, 300(1): F254-262.
5.	Jang HJ, Tsoyi K, Kim YM, et al. (S)-1-alpha-naphthylmethyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline (CKD712), promotes wound closure by producing VEGF through HO-1 induction in human dermal fibroblasts and mouse skin. Br J Pharmacol, 2013, 168(6): 1485-1496.
6.	Loboda A, Jazwa A, Grochot-Przeczek A, et al. Heme oxygenase-1 and the vascular bed: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal, 2008, 10(10): 1767-1812.
7.	Tesfay L, Huhn AJ, Hatcher H, et al. Ferritin blocks inhibitory effects of two-chain high molecular weight kininogen (HKa) on adhesion and survival signaling in endothelial cells. PLoS One, 2012, 7(7): e40030.
8.	Choi YK, Kim CK, Lee H, et al. Carbon monoxide promotes VEGF expression by increasing HIF-1alpha protein level via two distinct mechanisms, translational activation and stabilization of HIF-1alpha protein. J Biol Chem, 2010, 285(42): 32116-32125.
9.	Liu XM, Peyton KJ, Durante W. Physiological cyclic strain promotes endothelial cell survival via the induction of heme oxygenase-1. Am J Physiol Heart Circ Physiol, 2013, 304(12): H1634-1643.
10.	Shakeri-Manesch S, Zeyda M, Huber J, et al. Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance. Int J Obes (Lond), 2009, 33(11): 1257-1264.
11.	Zou YY, Kan EM, Lu J, et al. Primary blast injury-induced lesions in the retina of adult rats. J Neuroinflammation, 2013, 10: 79.
12.	Wu ML, Ho YC, Yet SF. A central role of heme oxygenase-1 in cardiovascular protection. Antioxid Redox Signal, 2011, 15(7): 1835-1846.
13.	Tenhunen R, Marver HS, Schmid R. The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin. J Lab Clin Med, 1970, 75(3): 410-421.
14.	Gabunia K, Ellison SP, Singh H, et al. Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells. J Biol Chem, 2012, 287(4): 2477-2484.
15.	Grochot-Przeczek A, Dulak J, Jozkowicz A. Haem oxygenase-1: non-canonical roles in physiology and pathology. Clin Sci (Lond), 2012, 122(3): 93-103.
16.	Kahlo K, Fill Malfertheiner S, Ignatov T, et al. HO-1 as modulator of the innate immune response in pregnancy. Am J Reprod Immunol, 2013, 70(1): 24-30.
17.	An L, Liu CT, Yu MJ, et al. Heme oxygenase-1 system, inflammation and ventilator-induced lung injury. Eur J Pharmacol, 2012, 677(1-3): 1-4.
18.	Otterbein LE, Zuckerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med, 2003, 9(2): 183-190.
19.	Sarady JK, Zuckerbraun BS, Bilban M, et al. Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J, 2004, 18(7): 854-856.
20.	Mancuso C, Barone E. The heme oxygenase/biliverdin reductase pathway in drug research and development. Curr Drug Metab, 2009, 10(6): 579-594.
21.	Marti HH, Risau W. Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci U S A, 1998, 95(26): 15809-15814.
22.	Giavazzi R, Sennino B, Coltrini D, et al. Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis. Am J Pathol, 2003, 162(6): 1913-1926.
23.	Deshane J, Chen S, Caballero S, et al. Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism. J Exp Med, 2007, 204(3): 605-618.
24.	Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation, 2004, 109(20): 2454-2461.
25.	Lin HH, Chen YH, Yet SF, et al. After vascular injury, heme oxygenase-1/carbon monoxide enhances re-endothelialization via promoting mobilization of circulating endothelial progenitor cells. J Thromb Haemost, 2009, 7(8): 1401-1408.
26.	Jozkowicz A, Cooke JP, Guevara I, et al. Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF. Cardiovasc Res, 2001, 51(4): 773-783.
27.	Marazioti A, Bucci M, Coletta C, et al. Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules. Arterioscler Thromb Vasc Biol, 2011, 31(11): 2570-2576.
28.	He M, Siow RC, Sugden D, et al. Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: a role for Nrf2 in vascular protection in diabetes. Nutr Metab Cardiovasc Dis, 2011, 21(4): 277-285.
29.	Wu KC, Mcdonald PR, Liu JJ, et al. Implementation of a high-throughput screen for identifying small molecules to activate the Keap1-Nrf2-ARE pathway. PLoS One, 2012, 7(10): e44686.
30.	Ferrando M, Gueron G, Elguero B, et al. Heme oxygenase 1 (HO- 1) challenges the angiogenic switch in prostate cancer. Angiogenesis, 2011, 14(4): 467-479.
31.	Guleng B, Tateishi K, Ohta M, et al. Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-independent manner. Cancer Res, 2005, 65(13): 5864-5871.
32.	徐卫华, 沈振亚. 慢病毒介导HO-1基因转染猪骨髓间充质干细胞的表达. 江苏医药, 2012, 38(15): 1750-1753.
33.	Hou C, Shen L, Huang Q, et al. The effect of heme oxygenase-1 complexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer. Biomaterials, 2013, 34(1): 112-120.
34.	Salgado AJ, Reis RL, Sousa NJ, et al. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther, 2010, 5(2): 103-110.
35.	Zuk P. Adipose-derived stem cells in tissue regeneration: a review. ISRN Stem Cells, 2013: 35.
36.	Doorn J, Moll G, Le Blanc K, et al. Therapeutic applications of mesenchymal stromal cells: paracrine effects and potential improvements. Tissue Eng Part B Rev, 2012, 18(2): 101-115.
37.	Stagg J, Galipeau J. Mechanisms of immune modulation by mesenchymal stromal cells and clinical translation. Curr Mol Med, 2013, 13(5): 856-867.
38.	Mougiakakos D, Jitschin R, Johansson CC, et al. The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells. Blood, 2011, 117(18): 4826-4835.
39.	Vanella L, Kim DH, Asprinio D, et al. HO-1 expression increases mesenchymal stem cell-derived osteoblasts but decreases adipocyte lineage. Bone, 2010, 46(1): 236-243.
40.	Vanella L, Sodhi K, Kim DH, et al. Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade. Stem Cell Res Ther, 2013, 4(2): 28.
41.	Zwerina J, Tzima S, Hayer S, et al. Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorption. FASEB J, 2005, 19(14): 2011-2013.
42.	Lin TH, Tang CH, Hung SY, et al. Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. J Cell Physiol, 2010, 222(3): 757-768.
43.	Yang JJ, Yang X, Liu ZQ, et al. Transplantation of adipose tissue-derived stem cells overexpressing heme oxygenase-1 improves functions and remodeling of infarcted myocardium in rabbits. Tohoku J Exp Med, 2012, 226(3): 231-241.
44.	陈学忠, 李志宏, 郭勇, 等. 大段组织工程骨的构建策略及存在的问题. 中华骨科杂志, 2011, 31(7): 811-814.
45.	楼晓莉, 陈江萍, 宋建星. 腺病毒介导VEGF和HO-1联合治疗缺血随意皮瓣的实验研究. 中国美容整形外科杂志, 2011, 22(6): 381-384.
46.	Jazwa A, Stepniewski J, Zamykal M, et al. Pre-emptive hypoxia-regulated HO-1 gene therapy improves post-ischaemic limb perfusion and tissue regeneration in mice. Cardiovasc Res, 2013, 97(1): 115-124.
47.	Chung J, Shin DY, Zheng M, et al. Carbon monoxide, a reaction product of heme oxygenase-1, suppresses the expression of C-reactive protein by endoplasmic reticulum stress through modulation of the unfolded protein response. Mol Immunol, 2011, 48(15-16): 1793-1799.

1. Evans CH. Gene delivery to bone. Advanced Drug Delivery Reviews, 2012, 64(12): 1331-1340.
2. 刘显挺, 江潞, 曾昕, 等. 调控VEGF的转录因子及其与肿瘤的关系. 中国肿瘤生物治疗杂志, 2010, 17(4): 468-472.
3. Kim YM, Pae HO, Park JE, et al. Heme oxygenase in the regulation of vascular biology: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal, 2011, 14(1): 137-167.
4. Zarjou A, Kim J, Traylor AM, et al. Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1. Am J Physiol Renal Physiol, 2011, 300(1): F254-262.
5. Jang HJ, Tsoyi K, Kim YM, et al. (S)-1-alpha-naphthylmethyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline (CKD712), promotes wound closure by producing VEGF through HO-1 induction in human dermal fibroblasts and mouse skin. Br J Pharmacol, 2013, 168(6): 1485-1496.
6. Loboda A, Jazwa A, Grochot-Przeczek A, et al. Heme oxygenase-1 and the vascular bed: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal, 2008, 10(10): 1767-1812.
7. Tesfay L, Huhn AJ, Hatcher H, et al. Ferritin blocks inhibitory effects of two-chain high molecular weight kininogen (HKa) on adhesion and survival signaling in endothelial cells. PLoS One, 2012, 7(7): e40030.
8. Choi YK, Kim CK, Lee H, et al. Carbon monoxide promotes VEGF expression by increasing HIF-1alpha protein level via two distinct mechanisms, translational activation and stabilization of HIF-1alpha protein. J Biol Chem, 2010, 285(42): 32116-32125.
9. Liu XM, Peyton KJ, Durante W. Physiological cyclic strain promotes endothelial cell survival via the induction of heme oxygenase-1. Am J Physiol Heart Circ Physiol, 2013, 304(12): H1634-1643.
10. Shakeri-Manesch S, Zeyda M, Huber J, et al. Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance. Int J Obes (Lond), 2009, 33(11): 1257-1264.
11. Zou YY, Kan EM, Lu J, et al. Primary blast injury-induced lesions in the retina of adult rats. J Neuroinflammation, 2013, 10: 79.
12. Wu ML, Ho YC, Yet SF. A central role of heme oxygenase-1 in cardiovascular protection. Antioxid Redox Signal, 2011, 15(7): 1835-1846.
13. Tenhunen R, Marver HS, Schmid R. The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin. J Lab Clin Med, 1970, 75(3): 410-421.
14. Gabunia K, Ellison SP, Singh H, et al. Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells. J Biol Chem, 2012, 287(4): 2477-2484.
15. Grochot-Przeczek A, Dulak J, Jozkowicz A. Haem oxygenase-1: non-canonical roles in physiology and pathology. Clin Sci (Lond), 2012, 122(3): 93-103.
16. Kahlo K, Fill Malfertheiner S, Ignatov T, et al. HO-1 as modulator of the innate immune response in pregnancy. Am J Reprod Immunol, 2013, 70(1): 24-30.
17. An L, Liu CT, Yu MJ, et al. Heme oxygenase-1 system, inflammation and ventilator-induced lung injury. Eur J Pharmacol, 2012, 677(1-3): 1-4.
18. Otterbein LE, Zuckerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med, 2003, 9(2): 183-190.
19. Sarady JK, Zuckerbraun BS, Bilban M, et al. Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J, 2004, 18(7): 854-856.
20. Mancuso C, Barone E. The heme oxygenase/biliverdin reductase pathway in drug research and development. Curr Drug Metab, 2009, 10(6): 579-594.
21. Marti HH, Risau W. Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci U S A, 1998, 95(26): 15809-15814.
22. Giavazzi R, Sennino B, Coltrini D, et al. Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis. Am J Pathol, 2003, 162(6): 1913-1926.
23. Deshane J, Chen S, Caballero S, et al. Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism. J Exp Med, 2007, 204(3): 605-618.
24. Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation, 2004, 109(20): 2454-2461.
25. Lin HH, Chen YH, Yet SF, et al. After vascular injury, heme oxygenase-1/carbon monoxide enhances re-endothelialization via promoting mobilization of circulating endothelial progenitor cells. J Thromb Haemost, 2009, 7(8): 1401-1408.
26. Jozkowicz A, Cooke JP, Guevara I, et al. Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF. Cardiovasc Res, 2001, 51(4): 773-783.
27. Marazioti A, Bucci M, Coletta C, et al. Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules. Arterioscler Thromb Vasc Biol, 2011, 31(11): 2570-2576.
28. He M, Siow RC, Sugden D, et al. Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: a role for Nrf2 in vascular protection in diabetes. Nutr Metab Cardiovasc Dis, 2011, 21(4): 277-285.
29. Wu KC, Mcdonald PR, Liu JJ, et al. Implementation of a high-throughput screen for identifying small molecules to activate the Keap1-Nrf2-ARE pathway. PLoS One, 2012, 7(10): e44686.
30. Ferrando M, Gueron G, Elguero B, et al. Heme oxygenase 1 (HO- 1) challenges the angiogenic switch in prostate cancer. Angiogenesis, 2011, 14(4): 467-479.
31. Guleng B, Tateishi K, Ohta M, et al. Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-independent manner. Cancer Res, 2005, 65(13): 5864-5871.
32. 徐卫华, 沈振亚. 慢病毒介导HO-1基因转染猪骨髓间充质干细胞的表达. 江苏医药, 2012, 38(15): 1750-1753.
33. Hou C, Shen L, Huang Q, et al. The effect of heme oxygenase-1 complexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer. Biomaterials, 2013, 34(1): 112-120.
34. Salgado AJ, Reis RL, Sousa NJ, et al. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther, 2010, 5(2): 103-110.
35. Zuk P. Adipose-derived stem cells in tissue regeneration: a review. ISRN Stem Cells, 2013: 35.
36. Doorn J, Moll G, Le Blanc K, et al. Therapeutic applications of mesenchymal stromal cells: paracrine effects and potential improvements. Tissue Eng Part B Rev, 2012, 18(2): 101-115.
37. Stagg J, Galipeau J. Mechanisms of immune modulation by mesenchymal stromal cells and clinical translation. Curr Mol Med, 2013, 13(5): 856-867.
38. Mougiakakos D, Jitschin R, Johansson CC, et al. The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells. Blood, 2011, 117(18): 4826-4835.
39. Vanella L, Kim DH, Asprinio D, et al. HO-1 expression increases mesenchymal stem cell-derived osteoblasts but decreases adipocyte lineage. Bone, 2010, 46(1): 236-243.
40. Vanella L, Sodhi K, Kim DH, et al. Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade. Stem Cell Res Ther, 2013, 4(2): 28.
41. Zwerina J, Tzima S, Hayer S, et al. Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorption. FASEB J, 2005, 19(14): 2011-2013.
42. Lin TH, Tang CH, Hung SY, et al. Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. J Cell Physiol, 2010, 222(3): 757-768.
43. Yang JJ, Yang X, Liu ZQ, et al. Transplantation of adipose tissue-derived stem cells overexpressing heme oxygenase-1 improves functions and remodeling of infarcted myocardium in rabbits. Tohoku J Exp Med, 2012, 226(3): 231-241.
44. 陈学忠, 李志宏, 郭勇, 等. 大段组织工程骨的构建策略及存在的问题. 中华骨科杂志, 2011, 31(7): 811-814.
45. 楼晓莉, 陈江萍, 宋建星. 腺病毒介导VEGF和HO-1联合治疗缺血随意皮瓣的实验研究. 中国美容整形外科杂志, 2011, 22(6): 381-384.
46. Jazwa A, Stepniewski J, Zamykal M, et al. Pre-emptive hypoxia-regulated HO-1 gene therapy improves post-ischaemic limb perfusion and tissue regeneration in mice. Cardiovasc Res, 2013, 97(1): 115-124.
47. Chung J, Shin DY, Zheng M, et al. Carbon monoxide, a reaction product of heme oxygenase-1, suppresses the expression of C-reactive protein by endoplasmic reticulum stress through modulation of the unfolded protein response. Mol Immunol, 2011, 48(15-16): 1793-1799.

Chinese Journal of Reparative and Reconstructive Surgery

RESEARCH PROGRESS OF HEME OXYGENASE 1 IN BONE TISSUE ENGINEERING

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