Flavonoid compound icariin activates hypoxia inducible factor-1α in chondrocytes and promotes articular cartilage repair

PLoS ONE

Volumn 11, Issue 2, 2016, Pages

  Wang, Pengzhen ^a,b   Zhang, Fengjie ^b,c   He, Qiling ^d   Wang, Jianqi ^b   Shiu, Hoi Ting ^c   Shu, Yinglan ^b,c   Tsang, Wing Pui ^b,c   Liang, Shuang ^b,c   Zhao, Kai ^b,c   Wan, Chao ^a,b,c  

^a JINAN UNIVERSITY   (China)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^c Prince of Wales Hospital   (Hong Kong)

^d University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (4,5 DIMETHYL 2 THIAZOLYL) 2,5 DIPHENYLTETRAZOLIUM BROMIDE; AGGRECAN; AGGRECANASE 1; BROXURIDINE; CELL NUCLEUS ANTIGEN; COLLAGEN TYPE 10; COLLAGEN TYPE 10ALPHA1; COLLAGEN TYPE 2; COLLAGEN TYPE 2ALPHA1; COLLAGENASE 3; CRE RECOMBINASE; FLAVONOID; GELATINASE A; GELATINASE B; HYPOXIA INDUCIBLE FACTOR 1ALPHA; ICARIIN; LUCIFERASE; MESSENGER RNA; TRANSCRIPTION FACTOR SOX9; UNCLASSIFIED DRUG; COL2A1 PROTEIN, MOUSE; DIFFERENTIATION ANTIGEN; HIF1A PROTEIN, MOUSE; SOX9 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOACCUMULATION; CARTILAGE CELL; CELL ASSAY; CELL DIFFERENTIATION; CHONDROGENESIS; COMPLEX FORMATION; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG RESPONSE; EXTRACELLULAR MATRIX; GENE FREQUENCY; IN VITRO STUDY; IN VIVO STUDY; LYMPHOCYTE COUNT; MALE; MOUSE; NONHUMAN; OSTEOCHONDRITIS; PHENOTYPE; PROTEIN EXPRESSION; PROTEOGLYCAN SYNTHESIS; REAL TIME POLYMERASE CHAIN REACTION; SCORING SYSTEM; SCREENING TEST; UPREGULATION; ANIMAL; BIOSYNTHESIS; CARTILAGE; CELL CULTURE; CELL NUCLEUS; CHONDROCYTE; DRUG EFFECTS; GENETICS; METABOLISM; NUCLEOCYTOPLASMIC TRANSPORT; PHYSIOLOGY; REGENERATION;

ACTIVE TRANSPORT, CELL NUCLEUS; ANIMALS; ANTIGENS, DIFFERENTIATION; CARTILAGE; CELL DIFFERENTIATION; CELL NUCLEUS; CELLS, CULTURED; CHONDROCYTES; COLLAGEN TYPE II; EXTRACELLULAR MATRIX; FLAVONOIDS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MICE; REGENERATION; SOX9 TRANSCRIPTION FACTOR; UP-REGULATION;

EID: 84959010959     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0148372     Document Type: Article

References (57)

1. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. (2015) Repair and tissue engineering technigues for articular cartilage. Nat Rev Rheumatol 11(1):21-34. doi: 10.1038/nrrheum.2014.157 PMID: 25247412
2. Hunziker EB. (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10(6):432-463. PMID: 12056848
3. Schindler OS. (2011) Current concepts of articular cartilage repair. Acta Orthop Belg 77 (6): 709-726. PMID: 22308614
4. Oldershaw RA. (2012) Cell sources for the regeneration of articular cartilage: the past, the horizon and the future. Int J Exp Pathol 93 (6): 389-400. doi: 10.1111/j.1365-2613.2012.00837.x PMID: 23075006
5. Tuan RS, Chen AF, Klatt BA. (2013) Cartilage regeneration. J Am Acad Orthop Surg 21 (5): 303-311.
6. Fan H, Tao H, Wu Y, Hu Y, Yan Y, Luo Z. (2010) TGF-beta 3 immobilized PLGA - gelatin/chondroitin sulfate/hyaluronic acid hybrid scaffold for cartilage regeneration. J Biomed Mater Res A 95(4): 982-92. doi: 10.1002/jbm.a.32899 PMID: 20872747
7. Yang HS, La WG, Bhang SH, Kim HJ, Im GI, Lee H, et al. (2011) Hyaline cartilage regeneration by combined therapy of microfracture and long-term bone morphogenetic protein-2 delivery. Tissue Eng Part A 17(13-14): 1809-18. doi: 10.1089/ten.TEA.2010.0540 PMID: 21366427
8. Lopiz-Morales Y, Abarrategi A, Ramos V, Moreno-Vicente C, Lopez-Duran L, Lopez-Lacomba JL, et al. (2010) In vivo comparison of the effects of rhBMP-2 and rhBMP-4 in osteochondral tissue regeneration. Eur Cell Mater 20: 367-78. PMID: 21154243
9. Danišovič L, Varga I, Polák S. (2012) Growth factors and chondrogenic differentiation of mesenchymal stem cells. Tissue Cell 44(2): 69-73. doi: 10.1016/j.tice.2011.11.005 PMID: 22185680
10. Tiwary R, Amarpal, Aithal HP, Kinjavdekar P, Pawde AM, Singh R. (2014) Effect of IGF-1 and uncultured autologous bone-marrow-derived mononuclear cells on repair of osteochondral defect in rabbits. Cartilage 5(1): 43-54. doi: 10.1177/1947603513499366 PMID: 26069684
11. Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF. (2010) Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells. Tissue Eng Part A 16(3): 1009-19. doi: 10.1089/ten.TEA.2009.0100 PMID: 19842915
12. Semenza GL. (2000) HIF-1 and human disease: one highly involved factor. Genes Dev 14: 1983-91. PMID: 10950862
13. Schofield CJ, Ratcliffe PJ. (2004) Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 5: 343-54. PMID: 15122348
14. Schipani E, Ryan HE, Didrickson S, Kobayashi T, Knight M, Johnson RS. (2001) Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev 15: 2865-2876. PMID: 11691837
15. Amarilio R, Viukov SV, Sharir A, Eshkar-Oren I, Johnson RS, Zelzer E. (2007) HIF1alpha regulation of Sox9 is necessary to maintain differentiation of hypoxic prechondrogenic cells during early skeletogenesis. Development 134: 3917-3928. PMID: 17913788
16. Pfander D, Cramer T, Schipani E, Johnson RS. (2003) HIF-1α controls extracellular matrix synthesis by epiphyseal chondrocytes. J Cell Sci 116: 1819-1826. PMID: 12665562
17. Ferguson C, Alpern E, Miclau T, Helms JA. (1999) Does adult fracture repair recapitulate embryonic skeletal formation? Mech Dev 87(1-2): 57-66. PMID: 10495271
18. Komatsu DE, Hadjiargyrou M. (2004) Activation of the transcription factor HIF-1 and its target genes, VEGF, HO-1, iNOS, during fracture repair. Bone 34(4): 680-8. PMID: 15050899
19. Wan C, Gilbert SR, Wang Y, Cao X, Shen X, Ramaswamy G, et al. (2008) Activation of the hypoxiainducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci U S A 105(2): 686-91. doi: 10.1073/pnas.0708474105 PMID: 18184809
20. Shen X, Wan C, Ramaswamy G, Mavalli M, Wang Y, Duvall CL, et al. (2009) Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J Orthop Res 27 (10): 1298-1305. doi: 10.1002/jor.20886 PMID: 19338032
21. Wan L, Zhang F, He Q, Tsang WP, Lu L, Li Q, et al. (2014) EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis. PLoS One 9(7): e102010. doi: 10.1371/journal.pone.0102010 PMID: 25003898
22. Fu Ji, Taubman MB. (2010) Prolyl hydroxylase EGLN3 regulates skeletal myoblast differentiation through an NF-kappaB-dependent pathway. J Biol Chem 285(12):8927-35. doi: 10.1074/jbc.M109. 078600 PMID: 20089853
23. Li TF, Chen D, Wu Q, Chen M, Sheu TJ, Schwarz EM, et al. (2006) Trans-forming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes. J Biol Chem 281(30): 21296-304. PMID: 16690606
24. Eltawil NM, De Bari C, Achan P, Pitzalis C, Dell'accio F. (2009) A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury. Osteoarthritis Cartilage 17 (6): 695-704. doi: 10.1016/j.joca.2008.11.003 PMID: 19070514
25. Mainil-Varlet P, Van Damme B, Nesic D, Knutsen G, Kandel R, Roberts S. (2010) A new histology scoring system for the assessment of the quality of human cartilage repair: ICRS II. Am J Sports Med 38(5): 880-90. doi: 10.1177/0363546509359068 PMID: 20203290
26. Park SS, Bae I, Lee YJ. (2008) Flavonoids-induced accumulation of hypoxia-inducible factor (HIF)-1alpha/2alpha is mediated through chelation of iron. J Cell Biochem 103(6):1989-98. PMID: 17973296
27. Leopoldini M, Russo N, Chiodo S, Toscano M. (2006) Iron chelation by the powerful antioxidant flavonoid quercetin. J Agric Food Chem 54: 6343-6351. PMID: 16910729
28. Brighton CT, Heppenstall RB. (1971) Oxygen tension in zones of the epiphyseal plate, the metaphysis and diaphysis. An in vitro and in vivo study in rats and rabbits. J Bone Joint Surg Am 53: 719-728. PMID: 5580029
29. Lund-Olesen K. (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13: 769-776. PMID: 5495389
30. Treuhaft PS, MC DJ. (1971) Synovial fluid pH, lactate, oxygen and carbon dioxide partial pressure in various joint diseases. Arthritis Rheum 14: 475-484. PMID: 5564921
31. Pfander D, Kobayashi T, Knight MC, Zelzer E, Chan DA, Olsen BR, et al. (2004) Deletion of Vhlh in chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development. Development 131: 2497-2508. PMID: 15128677
32. Stewart AJ, Houston B, Farquharson C. (2006) Elevated expression of hypoxia inducible factor-2alpha in terminally differentiating growth plate chondrocytes. J Cell Physiol 206: 435-440. PMID: 16155924
33. Provot S, Schipani E. (2007) Fetal growth plate: a developmental model of cellular adaptation to hypoxia. Ann N Y Acad Sci 1117: 26-39. PMID: 18056035
34. Gelse K, Pfander D, Obier S, Knaup KX, Wiesener M, Hennig FF, Swoboda B. (2008) The role of HIF-1alpha for the integrity of articular cartilage in murine knee joints. Arthritis Res Ther 10: R111.
35. Lafont JE, Talma S, Hopfgarten C, Murphy CL. (2008) Hypoxia promotes the differentiated human articular chondrocyte phenotype through SOX9-dependent and-independent pathways. J Biol Chem 283 (8): 4778-86. PMID: 18077449
36. Thoms BL, Dudek KA, Lafont JE, Murphy CL. (2013)nHypoxia promotes the production and inhibits the destruction of human articular cartilage. Arthritis Rheum 65(5): 1302-12.
37. Song YH, Cai H, Gu N, Qian CF, Cao SP, Zhao ZM. (2011) Icariin attenuates cardiac remodelling through down-regulating myocardial apoptosis and matrix metalloproteinase activity in rats with congestive heart failure. J Pharm Pharmacol. 63(4): 541-549. doi: 10.1111/j.2042-7158.2010.01241.x PMID: 21401606
38. Wang L, Zhang L, Chen ZB, Wu JY, Zhang X, Xu Y. (2009) Icariin enhances neuronal survival after oxygen and glucose deprivation by increasing SIRT1. Eur J Pharmacol 609: 40-44. doi: 10.1016/j.ejphar. 2009.03.033 PMID: 19303870
39. Cao H, Ke Y, Zhang Y, Zhang CJ, Qian W, Zhang GL. (2012) Icariin stimulates MC3T3-E1 cell proliferation and differentiation through up-regulation of bone morphogenetic protein-2. Int J Mol Med 29(3): 435-439. doi: 10.3892/ijmm.2011.845 PMID: 22109711
40. Zhao J, Ohba S, Komiyama Y, Shinkai M, Chung UI, Nagamune T. (2010) Icariin: a potential osteoinductive compound for bone tissue engineering. Tissue Eng Part A 16(1): 233-243. doi: 10.1089/ten. TEA.2009.0165 PMID: 19698057
41. Hsieh TP, Sheu SY, Sun JS, Chen MH, Liu MH. (2010) Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and Cbfa1 expression. Phytomedicine 17(6): 414-423. doi: 10.1016/j.phymed.2009.08.007 PMID: 19747809
42. Chen KM, Ge BF, Liu XY, Ma PH, Lu MB, Bai MH, et al. (2007) Icariin inhibits the osteoclast formation induced by RANKL and macrophage-colony stimulating factor in mouse bone marrow culture. Pharmazie 62 (5): 388-391. PMID: 17557750
43. Hsieh TP, Sheu SY, Sun JS, Chen MH. (2011) Icariin inhibits osteoclast differentiation and bone resorption by suppression of MAPKs/NF-κB regulated HIF-1 and PGE(2) synthesis. Phytomedicine 18 (2-3): 176-185.
44. Li B, Duan X, Xu C, Wu J, Liu B, Du Y, et al. (2014) Icariin attenuates glucocorticoid insensitivity mediated by repeated psychosocial stress on an ovalbumin-induced murine model of asthma. Int Immunopharmacol 19(2): 381-390. doi: 10.1016/j.intimp.2014.01.009 PMID: 24462390
45. Xu CQ, Liu BJ, Wu JF, Xu YC, Duan XH, Cao YX, et al. (2010) Icariin attenuates LPS-induced acute inflammatory responses: involvement of PI3K/Akt and NF-kappaB signaling pathway. Eur J Pharmacol 642(1e3): 146-153.
46. Li ZJ, Yao C, Liu SF, Chen L, Xi YM, Zhang W, Zhang GS. Cytotoxic effect of icaritin and its mechanisms in inducing apoptosis in human burkitt lymphoma cell line. Biomed Res Int. 2014; 2014:391512. doi: 10.1155/2014/391512 PMID: 24895574
47. Li D, Yuan T, Zhang X, Xiao Y, Wang R, Fan Y, et al. (2012) Icariin: a potential promoting compound for cartilage tissue engineering. Osteoarthritis Cartilage 20(12): 1647-1656. doi: 10.1016/j.joca.2012.08. 009 PMID: 22917745
48. Zhang L, Zhang X, Li KF, Li DX, Xiao YM, Fan YJ, et al. (2012) Icariin promotes extracellular matrix synthesis and gene expression of chondrocytes in vitro. Phytother Res 26(9): 1385-1392. doi: 10.1002/ptr.3733 PMID: 22308065
49. Liu MH, Sun JS, Tsai SW, Sheu SY, Chen MH. (2010) Icariin protects murine chondrocytes from lipopolysaccharide-induced inflammatory responses and extracellular matrix degradation. Nutr Res 30 (1):57-65. doi: 10.1016/j.nutres.2009.10.020 PMID: 20116661
50. Wang ZC, Sun HJ, Li KH, Fu C, Liu MZ. (2014) Icariin promotes directed chondrogenic differentiation of bone marrow mesenchymal stem cells but not hypertrophy in vitro. Exp Ther Med 8(5): 1528-1534. PMID: 25289054
51. Zhao J, Ohba S, Shinkai M, Chung UI, Nagamune T. (2008) Icariin induces osteogenic differentiation in vitro in a BMP and Runx2-dependent manner. Biochem Biophys Res Commun 369(2): 444-448.
52. Keith B, Johnson RS, Simon MC. (2011) HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 12(1):9-22. doi: 10.1038/nrc3183 PMID: 22169972
53. Hirao M, Tamai N, Tsumaki N, Yoshikawa H, Myoui A. (2006) Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. J Biol Chem 281:31079-31092. PMID: 16905540
54. Provot S, Zinyk D, Gunes Y, Kathri R, Le Q, Kronenberg HM, et al. (2007) Hif-1alpha regulates differentiation of limb bud mesenchyme and joint development. J Cell Biol 177(3):451-464. PMID: 17470636
55. Yang S, Kim J, Ryu JH, Oh H, Chun CH, Kim BJ, Min BH, Chun JS. (2010) Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med 16(6):687-93. doi: 10.1038/nm.2153 PMID: 20495569
56. Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H. (2010) Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16 (6):678-86. doi: 10.1038/nm.2146 PMID: 20495570
57. Araldi E, Khatri R, Giaccia AJ, Simon MC, Schipani E. (2011) Lack of HIF-2α in limb bud mesenchyme causes a modest and transient delay of endochondral bone development. Nat Med 17(1):25-26. doi: 10.1038/nm0111-25 PMID: 21217667