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Published in: BMC Musculoskeletal Disorders 1/2018

Open Access 01-12-2018 | Research article

Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis

Authors: Shotaro Takano, Kentaro Uchida, Gen Inoue, Toshihide Matsumoto, Jun Aikawa, Dai Iwase, Manabu Mukai, Masayuki Miyagi, Masashi Takaso

Published in: BMC Musculoskeletal Disorders | Issue 1/2018

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Abstract

Background

Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear.

Methods

We harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence [K/L] grade 2–4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF.

Results

VEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle.

Conclusion

Synovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.
Literature
1.
go back to reference Ayis S, Dieppe P. The natural history of disability and its determinants in adults with lower limb musculoskeletal pain. J Rheumatol. 2009;36(3):583–91.CrossRefPubMed Ayis S, Dieppe P. The natural history of disability and its determinants in adults with lower limb musculoskeletal pain. J Rheumatol. 2009;36(3):583–91.CrossRefPubMed
2.
go back to reference Dominick KL, Ahern FM, Gold CH, Heller DA. Health-related quality of life and health service use among older adults with osteoarthritis. Arthritis Rheum. 2004;51(3):326–31.CrossRefPubMed Dominick KL, Ahern FM, Gold CH, Heller DA. Health-related quality of life and health service use among older adults with osteoarthritis. Arthritis Rheum. 2004;51(3):326–31.CrossRefPubMed
3.
5.
go back to reference Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PW, Kelly-Hayes M, Wolf PA, Kreger BE, Kannel WB. The effects of specific medical conditions on the functional limitations of elders in the Framingham study. Am J Public Health. 1994;84(3):351–8.CrossRefPubMedPubMedCentral Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PW, Kelly-Hayes M, Wolf PA, Kreger BE, Kannel WB. The effects of specific medical conditions on the functional limitations of elders in the Framingham study. Am J Public Health. 1994;84(3):351–8.CrossRefPubMedPubMedCentral
6.
go back to reference Johnsen SP, Larsson H, Tarone RE, McLaughlin JK, Norgard B, Friis S, Sorensen HT. Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study. Arch Intern Med. 2005;165(9):978–84.CrossRefPubMed Johnsen SP, Larsson H, Tarone RE, McLaughlin JK, Norgard B, Friis S, Sorensen HT. Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study. Arch Intern Med. 2005;165(9):978–84.CrossRefPubMed
7.
go back to reference Whelton A. Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics. Am J Ther. 2000;7(2):63–74.CrossRefPubMed Whelton A. Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics. Am J Ther. 2000;7(2):63–74.CrossRefPubMed
8.
go back to reference Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter KC, Harris AL, Koukourakis MI. Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2003;5(4):R193–201.CrossRefPubMedPubMedCentral Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter KC, Harris AL, Koukourakis MI. Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2003;5(4):R193–201.CrossRefPubMedPubMedCentral
9.
go back to reference Haywood L, McWilliams DF, Pearson CI, Gill SE, Ganesan A, Wilson D, Walsh DA. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum. 2003;48(8):2173–7.CrossRefPubMed Haywood L, McWilliams DF, Pearson CI, Gill SE, Ganesan A, Wilson D, Walsh DA. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum. 2003;48(8):2173–7.CrossRefPubMed
10.
go back to reference Jackson JR, Minton JA, Ho ML, Wei N, Winkler JD. Expression of vascular endothelial growth factor in synovial fibroblasts is induced by hypoxia and interleukin 1beta. J Rheumatol. 1997;24(7):1253–9.PubMed Jackson JR, Minton JA, Ho ML, Wei N, Winkler JD. Expression of vascular endothelial growth factor in synovial fibroblasts is induced by hypoxia and interleukin 1beta. J Rheumatol. 1997;24(7):1253–9.PubMed
11.
go back to reference Lambert C, Mathy-Hartert M, Dubuc JE, Montell E, Verges J, Munaut C, Noel A, Henrotin Y. Characterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate. Arthritis Res Ther. 2012;14(2):R58.CrossRefPubMedPubMedCentral Lambert C, Mathy-Hartert M, Dubuc JE, Montell E, Verges J, Munaut C, Noel A, Henrotin Y. Characterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate. Arthritis Res Ther. 2012;14(2):R58.CrossRefPubMedPubMedCentral
12.
go back to reference Corrado A, Neve A, Cantatore FP. Expression of vascular endothelial growth factor in normal, osteoarthritic and osteoporotic osteoblasts. Clin Exp Med. 2013;13(1):81–4.CrossRefPubMed Corrado A, Neve A, Cantatore FP. Expression of vascular endothelial growth factor in normal, osteoarthritic and osteoporotic osteoblasts. Clin Exp Med. 2013;13(1):81–4.CrossRefPubMed
13.
go back to reference Huh JE, Seo DM, Baek YH, Choi DY, Park DS, Lee JD. Biphasic positive effect of formononetin on metabolic activity of human normal and osteoarthritic subchondral osteoblasts. Int Immunopharmacol. 2010;10(4):500–7.CrossRefPubMed Huh JE, Seo DM, Baek YH, Choi DY, Park DS, Lee JD. Biphasic positive effect of formononetin on metabolic activity of human normal and osteoarthritic subchondral osteoblasts. Int Immunopharmacol. 2010;10(4):500–7.CrossRefPubMed
14.
go back to reference Neve A, Cantatore FP, Corrado A, Gaudio A, Ruggieri S, Ribatti D. In vitro and in vivo angiogenic activity of osteoarthritic and osteoporotic osteoblasts is modulated by VEGF and vitamin D3 treatment. Regul Pept. 2013;184:81–4.CrossRefPubMed Neve A, Cantatore FP, Corrado A, Gaudio A, Ruggieri S, Ribatti D. In vitro and in vivo angiogenic activity of osteoarthritic and osteoporotic osteoblasts is modulated by VEGF and vitamin D3 treatment. Regul Pept. 2013;184:81–4.CrossRefPubMed
15.
go back to reference Fay J, Varoga D, Wruck CJ, Kurz B, Goldring MB, Pufe T. Reactive oxygen species induce expression of vascular endothelial growth factor in chondrocytes and human articular cartilage explants. Arthritis Res Ther. 2006;8(6):R189.CrossRefPubMedPubMedCentral Fay J, Varoga D, Wruck CJ, Kurz B, Goldring MB, Pufe T. Reactive oxygen species induce expression of vascular endothelial growth factor in chondrocytes and human articular cartilage explants. Arthritis Res Ther. 2006;8(6):R189.CrossRefPubMedPubMedCentral
16.
go back to reference Mabey T, Honsawek S, Saetan N, Poovorawan Y, Tanavalee A, Yuktanandana P. Angiogenic cytokine expression profiles in plasma and synovial fluid of primary knee osteoarthritis. Int Orthop. 2014;38(9):1885–92.CrossRefPubMed Mabey T, Honsawek S, Saetan N, Poovorawan Y, Tanavalee A, Yuktanandana P. Angiogenic cytokine expression profiles in plasma and synovial fluid of primary knee osteoarthritis. Int Orthop. 2014;38(9):1885–92.CrossRefPubMed
17.
go back to reference Saetan N, Honsawek S, Tanavalee A, Yuktanandana P, Meknavin S, Ngarmukos S, Tanpowpong T, Parkpian V. Relationship of plasma and synovial fluid vascular endothelial growth factor with radiographic severity in primary knee osteoarthritis. Int Orthop. 2014;38(5):1099–104.CrossRefPubMed Saetan N, Honsawek S, Tanavalee A, Yuktanandana P, Meknavin S, Ngarmukos S, Tanpowpong T, Parkpian V. Relationship of plasma and synovial fluid vascular endothelial growth factor with radiographic severity in primary knee osteoarthritis. Int Orthop. 2014;38(5):1099–104.CrossRefPubMed
18.
go back to reference Sohn DH, Sokolove J, Sharpe O, Erhart JC, Chandra PE, Lahey LJ, Lindstrom TM, Hwang I, Boyer KA, Andriacchi TP, Robinson WH. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via toll-like receptor 4. Arthritis Res Ther. 2012;14(1):R7.CrossRefPubMedPubMedCentral Sohn DH, Sokolove J, Sharpe O, Erhart JC, Chandra PE, Lahey LJ, Lindstrom TM, Hwang I, Boyer KA, Andriacchi TP, Robinson WH. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via toll-like receptor 4. Arthritis Res Ther. 2012;14(1):R7.CrossRefPubMedPubMedCentral
19.
go back to reference Ballara S, Taylor PC, Reusch P, Marme D, Feldmann M, Maini RN, Paleolog EM. Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum. 2001;44(9):2055–64.CrossRefPubMed Ballara S, Taylor PC, Reusch P, Marme D, Feldmann M, Maini RN, Paleolog EM. Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum. 2001;44(9):2055–64.CrossRefPubMed
20.
go back to reference Cui RR, Mao DA, Yi L, Wang C, Zhang XX, Xie H, Wu XP, Liao XB, Zhou H, Meng JC, Yuan LQ, Liao EY. Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways. Amino Acids. 2010;39(5):1193–200.CrossRefPubMed Cui RR, Mao DA, Yi L, Wang C, Zhang XX, Xie H, Wu XP, Liao XB, Zhou H, Meng JC, Yuan LQ, Liao EY. Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways. Amino Acids. 2010;39(5):1193–200.CrossRefPubMed
21.
go back to reference Lv S, Yang YJ, Hong S, Wang N, Qin Y, Li W, Chen Q. Intrathecal apelin-13 produced different actions in formalin test and tail-flick test in mice. Protein Pept Lett. 2013;20(8):926–31.CrossRefPubMed Lv S, Yang YJ, Hong S, Wang N, Qin Y, Li W, Chen Q. Intrathecal apelin-13 produced different actions in formalin test and tail-flick test in mice. Protein Pept Lett. 2013;20(8):926–31.CrossRefPubMed
22.
go back to reference Lv SY, Qin YJ, Wang NB, Yang YJ, Chen Q. Supraspinal antinociceptive effect of apelin-13 in a mouse visceral pain model. Peptides. 2012;37(1):165–70.CrossRefPubMed Lv SY, Qin YJ, Wang NB, Yang YJ, Chen Q. Supraspinal antinociceptive effect of apelin-13 in a mouse visceral pain model. Peptides. 2012;37(1):165–70.CrossRefPubMed
23.
go back to reference Perjes A, Skoumal R, Tenhunen O, Konyi A, Simon M, Horvath IG, Kerkela R, Ruskoaho H, Szokodi I. Apelin increases cardiac contractility via protein kinase Cepsilon- and extracellular signal-regulated kinase-dependent mechanisms. PLoS One. 2014;9(4):e93473.CrossRefPubMedPubMedCentral Perjes A, Skoumal R, Tenhunen O, Konyi A, Simon M, Horvath IG, Kerkela R, Ruskoaho H, Szokodi I. Apelin increases cardiac contractility via protein kinase Cepsilon- and extracellular signal-regulated kinase-dependent mechanisms. PLoS One. 2014;9(4):e93473.CrossRefPubMedPubMedCentral
24.
go back to reference Reaux A, Gallatz K, Palkovits M, Llorens-Cortes C. Distribution of apelin-synthesizing neurons in the adult rat brain. Neuroscience. 2002;113(3):653–62.CrossRefPubMed Reaux A, Gallatz K, Palkovits M, Llorens-Cortes C. Distribution of apelin-synthesizing neurons in the adult rat brain. Neuroscience. 2002;113(3):653–62.CrossRefPubMed
25.
go back to reference Reaux A, De MN, Skultetyova I, Lenkei Z, El MS, Gallatz K, Corvol P, Palkovits M, Llorens-Cortes C. Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. J Neurochem. 2001;77(4):1085–96.CrossRefPubMed Reaux A, De MN, Skultetyova I, Lenkei Z, El MS, Gallatz K, Corvol P, Palkovits M, Llorens-Cortes C. Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. J Neurochem. 2001;77(4):1085–96.CrossRefPubMed
26.
go back to reference Smith TP, Schlenz AM, Schatz JC, Maitra R, Sweitzer SM. Modulation of pain in pediatric sickle cell disease: understanding the balance between endothelin mediated vasoconstriction and apelin mediated vasodilation. Blood Cells Mol Dis. 2015;54(2):155–9.CrossRefPubMed Smith TP, Schlenz AM, Schatz JC, Maitra R, Sweitzer SM. Modulation of pain in pediatric sickle cell disease: understanding the balance between endothelin mediated vasoconstriction and apelin mediated vasodilation. Blood Cells Mol Dis. 2015;54(2):155–9.CrossRefPubMed
27.
go back to reference Than A, Cheng Y, Foh LC, Leow MK, Lim SC, Chuah YJ, Kang Y, Chen P. Apelin inhibits adipogenesis and lipolysis through distinct molecular pathways. Mol Cell Endocrinol. 2012;362(1–2):227–41.CrossRefPubMed Than A, Cheng Y, Foh LC, Leow MK, Lim SC, Chuah YJ, Kang Y, Chen P. Apelin inhibits adipogenesis and lipolysis through distinct molecular pathways. Mol Cell Endocrinol. 2012;362(1–2):227–41.CrossRefPubMed
28.
go back to reference Xu N, Wang H, Fan L, Chen Q. Supraspinal administration of apelin-13 induces antinociception via the opioid receptor in mice. Peptides. 2009;30(6):1153–7.CrossRefPubMed Xu N, Wang H, Fan L, Chen Q. Supraspinal administration of apelin-13 induces antinociception via the opioid receptor in mice. Peptides. 2009;30(6):1153–7.CrossRefPubMed
29.
go back to reference Giatromanolaki A, Sivridis E, Athanassou N, Zois E, Thorpe PE, Brekken RA, Gatter KC, Harris AL, Koukourakis IM, Koukourakis MI. The angiogenic pathway “vascular endothelial growth factor/flk-1(KDR)-receptor” in rheumatoid arthritis and osteoarthritis. J Pathol. 2001;194(1):101–8.CrossRefPubMed Giatromanolaki A, Sivridis E, Athanassou N, Zois E, Thorpe PE, Brekken RA, Gatter KC, Harris AL, Koukourakis IM, Koukourakis MI. The angiogenic pathway “vascular endothelial growth factor/flk-1(KDR)-receptor” in rheumatoid arthritis and osteoarthritis. J Pathol. 2001;194(1):101–8.CrossRefPubMed
30.
go back to reference Nagai T, Sato M, Kobayashi M, Yokoyama M, Tani Y, Mochida J. Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis. Arthritis Res Ther. 2014;16(5):427.CrossRefPubMedPubMedCentral Nagai T, Sato M, Kobayashi M, Yokoyama M, Tani Y, Mochida J. Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis. Arthritis Res Ther. 2014;16(5):427.CrossRefPubMedPubMedCentral
31.
go back to reference Kiguchi N, Kobayashi Y, Kadowaki Y, Fukazawa Y, Saika F, Kishioka S. Vascular endothelial growth factor signaling in injured nerves underlies peripheral sensitization in neuropathic pain. J Neurochem. 2014;129(1):169–78.CrossRefPubMed Kiguchi N, Kobayashi Y, Kadowaki Y, Fukazawa Y, Saika F, Kishioka S. Vascular endothelial growth factor signaling in injured nerves underlies peripheral sensitization in neuropathic pain. J Neurochem. 2014;129(1):169–78.CrossRefPubMed
32.
go back to reference Lin J, Li G, Den X, Xu C, Liu S, Gao Y, Liu H, Zhang J, Li X, Liang S. VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X(2)(/)(3) receptor of primary sensory neurons. Brain Res Bull. 2010;83(5):284–91.CrossRefPubMed Lin J, Li G, Den X, Xu C, Liu S, Gao Y, Liu H, Zhang J, Li X, Liang S. VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X(2)(/)(3) receptor of primary sensory neurons. Brain Res Bull. 2010;83(5):284–91.CrossRefPubMed
33.
go back to reference Liu S, Xu C, Li G, Liu H, Xie J, Tu G, Peng H, Qiu S, Liang S. Vatalanib decrease the positive interaction of VEGF receptor-2 and P2X2/3 receptor in chronic constriction injury rats. Neurochem Int. 2012;60(6):565–72.CrossRefPubMed Liu S, Xu C, Li G, Liu H, Xie J, Tu G, Peng H, Qiu S, Liang S. Vatalanib decrease the positive interaction of VEGF receptor-2 and P2X2/3 receptor in chronic constriction injury rats. Neurochem Int. 2012;60(6):565–72.CrossRefPubMed
34.
go back to reference Malykhina AP, Lei Q, Erickson CS, Epstein ML, Saban MR, Davis CA, Saban R. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity. BMC Physiol. 2012;12:15.CrossRefPubMedPubMedCentral Malykhina AP, Lei Q, Erickson CS, Epstein ML, Saban MR, Davis CA, Saban R. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity. BMC Physiol. 2012;12:15.CrossRefPubMedPubMedCentral
35.
go back to reference Selvaraj D, Gangadharan V, Michalski CW, Kurejova M, Stosser S, Srivastava K, Schweizerhof M, Waltenberger J, Ferrara N, Heppenstall P, Shibuya M, Augustin HG, Kuner R. A functional role for VEGFR1 expressed in peripheral sensory neurons in Cancer pain. Cancer Cell. 2015;27(6):780–96.CrossRefPubMedPubMedCentral Selvaraj D, Gangadharan V, Michalski CW, Kurejova M, Stosser S, Srivastava K, Schweizerhof M, Waltenberger J, Ferrara N, Heppenstall P, Shibuya M, Augustin HG, Kuner R. A functional role for VEGFR1 expressed in peripheral sensory neurons in Cancer pain. Cancer Cell. 2015;27(6):780–96.CrossRefPubMedPubMedCentral
36.
go back to reference Takano S, Uchida K, Miyagi M, Inoue G, Fujimaki H, Aikawa J, Iwase D, Minatani A, Iwabuchi K, Takaso M. Nerve growth factor regulation by TNF-alpha and IL-1beta in synovial macrophages and fibroblasts in osteoarthritic mice. J Immunol Res. 2016;2016:5706359.CrossRefPubMedPubMedCentral Takano S, Uchida K, Miyagi M, Inoue G, Fujimaki H, Aikawa J, Iwase D, Minatani A, Iwabuchi K, Takaso M. Nerve growth factor regulation by TNF-alpha and IL-1beta in synovial macrophages and fibroblasts in osteoarthritic mice. J Immunol Res. 2016;2016:5706359.CrossRefPubMedPubMedCentral
37.
go back to reference Takano S, Uchida K, Miyagi M, Inoue G, Aikawa J, Fujimaki H, Minatani A, Sato M, Iwabuchi K, Takaso M. Synovial macrophage-derived IL-1beta regulates the calcitonin receptor in osteoarthritic mice. Clin Exp Immunol. 2016;183(1):143–9.CrossRefPubMed Takano S, Uchida K, Miyagi M, Inoue G, Aikawa J, Fujimaki H, Minatani A, Sato M, Iwabuchi K, Takaso M. Synovial macrophage-derived IL-1beta regulates the calcitonin receptor in osteoarthritic mice. Clin Exp Immunol. 2016;183(1):143–9.CrossRefPubMed
38.
go back to reference Takano S, Uchida K, Inoue G, Miyagi M, Aikawa J, Iwase D, Iwabuchi K, Matsumoto T, Satoh M, Mukai M, Minatani A, Takaso M. Nerve growth factor regulation and production by macrophages in osteoarthritic synovium. Clin Exp Immunol. 2017;190:235–43.CrossRefPubMed Takano S, Uchida K, Inoue G, Miyagi M, Aikawa J, Iwase D, Iwabuchi K, Matsumoto T, Satoh M, Mukai M, Minatani A, Takaso M. Nerve growth factor regulation and production by macrophages in osteoarthritic synovium. Clin Exp Immunol. 2017;190:235–43.CrossRefPubMed
39.
go back to reference Takano S, Uchida K, Inoue G, Minatani A, Miyagi M, Aikawa J, Iwase D, Onuma K, Mukai M, Takaso M. Increase and regulation of synovial calcitonin gene-related peptide expression in patients with painful knee osteoarthritis. J Pain Res. 2017;10:1099–104.CrossRefPubMedPubMedCentral Takano S, Uchida K, Inoue G, Minatani A, Miyagi M, Aikawa J, Iwase D, Onuma K, Mukai M, Takaso M. Increase and regulation of synovial calcitonin gene-related peptide expression in patients with painful knee osteoarthritis. J Pain Res. 2017;10:1099–104.CrossRefPubMedPubMedCentral
40.
go back to reference Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998;251(2):471–6.CrossRefPubMed Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998;251(2):471–6.CrossRefPubMed
41.
go back to reference Kunduzova O, Alet N, esque-Touchard N, Millet L, Castan-Laurell I, Muller C, Dray C, Schaeffer P, Herault JP, Savi P, Bono F, Valet P. Apelin/APJ signaling system: a potential link between adipose tissue and endothelial angiogenic processes. FASEB J. 2008;22(12):4146–53.CrossRefPubMed Kunduzova O, Alet N, esque-Touchard N, Millet L, Castan-Laurell I, Muller C, Dray C, Schaeffer P, Herault JP, Savi P, Bono F, Valet P. Apelin/APJ signaling system: a potential link between adipose tissue and endothelial angiogenic processes. FASEB J. 2008;22(12):4146–53.CrossRefPubMed
43.
go back to reference Xiong Q, He W, Wang H, Zhou J, Zhang Y, He J, Yang C, Zhang B. Effect of the spinal apelinAPJ system on the pathogenesis of chronic constriction injuryinduced neuropathic pain in rats. Mol Med Rep. 2017;16:1223–31.CrossRefPubMedPubMedCentral Xiong Q, He W, Wang H, Zhou J, Zhang Y, He J, Yang C, Zhang B. Effect of the spinal apelinAPJ system on the pathogenesis of chronic constriction injuryinduced neuropathic pain in rats. Mol Med Rep. 2017;16:1223–31.CrossRefPubMedPubMedCentral
44.
go back to reference Hu PF, Tang JL, Chen WP, Bao JP, Wu LD. Increased apelin serum levels and expression in human chondrocytes in osteoarthritic patients. Int Orthop. 2011;35(9):1421–6.CrossRefPubMed Hu PF, Tang JL, Chen WP, Bao JP, Wu LD. Increased apelin serum levels and expression in human chondrocytes in osteoarthritic patients. Int Orthop. 2011;35(9):1421–6.CrossRefPubMed
45.
go back to reference Minatani A, Uchida K, Inoue G, Takano S, Aikawa J, Miyagi M, Fujimaki H, Iwase D, Onuma K, Matsumoto T, Takaso M. Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1/EP2/EP4 receptor pathway in synovium of knee osteoarthritis patients. J Orthop Surg Res. 2016;11(1):117.CrossRefPubMedPubMedCentral Minatani A, Uchida K, Inoue G, Takano S, Aikawa J, Miyagi M, Fujimaki H, Iwase D, Onuma K, Matsumoto T, Takaso M. Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1/EP2/EP4 receptor pathway in synovium of knee osteoarthritis patients. J Orthop Surg Res. 2016;11(1):117.CrossRefPubMedPubMedCentral
46.
go back to reference Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain. 1997;72(1–2):95–7.CrossRefPubMed Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain. 1997;72(1–2):95–7.CrossRefPubMed
47.
go back to reference rendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149(3):573–81.CrossRef rendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149(3):573–81.CrossRef
48.
go back to reference Uchida K, Takano S, Matsumoto T, Nagura N, Inoue G, Itakura M, Miyagi M, Aikawa J, Iwase D, Minatani A, Fujimaki H, Takaso M. Transforming growth factor activating kinase 1 regulates extracellular matrix degrading enzymes and pain-related molecule expression following tumor necrosis factor-alpha stimulation of synovial cells: an in vitro study. BMC Musculoskelet Disord. 2017;18(1):283.CrossRefPubMedPubMedCentral Uchida K, Takano S, Matsumoto T, Nagura N, Inoue G, Itakura M, Miyagi M, Aikawa J, Iwase D, Minatani A, Fujimaki H, Takaso M. Transforming growth factor activating kinase 1 regulates extracellular matrix degrading enzymes and pain-related molecule expression following tumor necrosis factor-alpha stimulation of synovial cells: an in vitro study. BMC Musculoskelet Disord. 2017;18(1):283.CrossRefPubMedPubMedCentral
49.
go back to reference Nesic O, Sundberg LM, Herrera JJ, Mokkapati VU, Lee J, Narayana PA. Vascular endothelial growth factor and spinal cord injury pain. J Neurotrauma. 2010;27(10):1793–803.CrossRefPubMedPubMedCentral Nesic O, Sundberg LM, Herrera JJ, Mokkapati VU, Lee J, Narayana PA. Vascular endothelial growth factor and spinal cord injury pain. J Neurotrauma. 2010;27(10):1793–803.CrossRefPubMedPubMedCentral
50.
go back to reference Kasai A, Shintani N, Oda M, Kakuda M, Hashimoto H, Matsuda T, Hinuma S, Baba A. Apelin is a novel angiogenic factor in retinal endothelial cells. Biochem Biophys Res Commun. 2004;325(2):395–400.CrossRefPubMed Kasai A, Shintani N, Oda M, Kakuda M, Hashimoto H, Matsuda T, Hinuma S, Baba A. Apelin is a novel angiogenic factor in retinal endothelial cells. Biochem Biophys Res Commun. 2004;325(2):395–400.CrossRefPubMed
51.
go back to reference Zhao T, Lu Q, Tao Y, Liang XY, Wang K, Jiang YR. Effects of apelin and vascular endothelial growth factor on central retinal vein occlusion in monkey eyes intravitreally injected with bevacizumab: a preliminary study. Mol Vis. 2011;17:1044–55.PubMedPubMedCentral Zhao T, Lu Q, Tao Y, Liang XY, Wang K, Jiang YR. Effects of apelin and vascular endothelial growth factor on central retinal vein occlusion in monkey eyes intravitreally injected with bevacizumab: a preliminary study. Mol Vis. 2011;17:1044–55.PubMedPubMedCentral
52.
go back to reference Kawamata Y, Habata Y, Fukusumi S, Hosoya M, Fujii R, Hinuma S, Nishizawa N, Kitada C, Onda H, Nishimura O, Fujino M. Molecular properties of apelin: tissue distribution and receptor binding. Biochim Biophys Acta. 2001;1538(2–3):162–71.CrossRefPubMed Kawamata Y, Habata Y, Fukusumi S, Hosoya M, Fujii R, Hinuma S, Nishizawa N, Kitada C, Onda H, Nishimura O, Fujino M. Molecular properties of apelin: tissue distribution and receptor binding. Biochim Biophys Acta. 2001;1538(2–3):162–71.CrossRefPubMed
53.
go back to reference Medhurst AD, Jennings CA, Robbins MJ, Davis RP, Ellis C, Winborn KY, Lawrie KW, Hervieu G, Riley G, Bolaky JE, Herrity NC, Murdock P, Darker JG. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. J Neurochem. 2003;84(5):1162–72.CrossRefPubMed Medhurst AD, Jennings CA, Robbins MJ, Davis RP, Ellis C, Winborn KY, Lawrie KW, Hervieu G, Riley G, Bolaky JE, Herrity NC, Murdock P, Darker JG. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. J Neurochem. 2003;84(5):1162–72.CrossRefPubMed
Metadata
Title
Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis
Authors
Shotaro Takano
Kentaro Uchida
Gen Inoue
Toshihide Matsumoto
Jun Aikawa
Dai Iwase
Manabu Mukai
Masayuki Miyagi
Masashi Takaso
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2018
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-018-2127-2

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