Characterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate

被引:43
|
作者
Lambert, Cecile [1 ]
Mathy-Hartert, Marianne [1 ]
Dubuc, Jean-Emile [2 ]
Montell, Eulalia [3 ]
Verges, Josep [3 ]
Munaut, Carine [4 ]
Noel, Agnes [4 ]
Henrotin, Yves [1 ]
机构
[1] CHU Sart Tilman, Inst Pathol, Bone & Cartilage Res Unit, B-4000 Liege, Belgium
[2] Clin Univ St Luc, Dept Orthopaed, B-1200 Brussels, Belgium
[3] Bioiberica SA, Dept Med Sci, Pharmacol Res Unit, Barcelona 08029, Spain
[4] Univ Liege, Inst Pathol, Lab Tumor & Dev Biol, GIGA Canc, B-4000 Liege, Belgium
关键词
ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; PLACEBO-CONTROLLED TRIALS; RHEUMATOID-ARTHRITIS; KNEE OSTEOARTHRITIS; EXPRESSION; METAANALYSIS; INTERLEUKIN-1-BETA; INFLAMMATION; GLUCOSAMINE;
D O I
10.1186/ar3771
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: This work aimed at comparing the production of inflammatory and pro-and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane. The effects of interleukin (IL)-1 beta and chondroitin sulfate (CS) on the expression of pro-and anti-angiogenic factors by synovial fibroblasts cells (SFC) were also studied. Methods: Biopsies from N/R or from I areas of osteoarthritic synovial membrane were collected at the time of surgery. The inflammatory status of the synovial membrane was characterized by the surgeon according to macroscopic criteria, including the synovial vascularization, the villi formation and the hypertrophic aspect of the tissue. We assessed the expression of CD45, von Willebrand factor and vascular endothelial growth factor (VEGF) antigen by immunohistochemistry in both N/R and I biopsies. The production of IL-6, -8, VEGF and thrombospondin (TSP)-1 by N/R or I synovial cells was quantified by ELISA. SFC were cultured in the absence or in the presence of IL-1 beta (1 ng/ml) and with or without CS (10, 50, 200 mu g/ml). Gene expression of pro-angiogenic factors (VEGF, basic fibroblast growth factor (bFGF), nerve growth factor (NGF), matrix metalloproteinase (MMP)-2 and angiopoietin (ang)-1) and anti-angiogenic factors (vascular endothelial growth inhibitor (VEGI), TSP-1 and -2) were determined by real time RT-PCR. Production of VEGI and TSP-1 was also estimated by ELISA. Results: Immunohistochemistry showed the increase of lymphocyte infiltration, vascular density and VEGF expression in I compared to N/R synovial biopsies. Synovial cells from I areas produced more IL-6, IL-8 and VEGF but less TSP-1 than cells isolated from N/R synovial biopsies. The expression of pro-angiogenic factors by SFC was stimulated by IL-1 beta. A time dependent regulation of the expression of anti-angiogenic factor genes was observed. IL-1 beta stimulated the expression of anti-angiogenic factor genes but inhibited it after 24 h. CS reversed the inhibitory effect of IL-1 beta on anti-angiogenic factors, VEGI and TSP-1. Conclusions: We demonstrated that synovial biopsies from I areas expressed a pro-angiogenic phenotype. IL-1 beta induced an imbalance between pro-and anti-angiogenic factors in SFC and CS tended to normalize this IL-1 beta-induced imbalance, providing a new possible mechanism of action of this drug.
引用
收藏
页数:11
相关论文
共 50 条
  • [41] Chondroitin sulfate is superior to placebo in symptomatic knee osteoarthritis
    Lee, Young Ho
    ANNALS OF THE RHEUMATIC DISEASES, 2018, 77 (08)
  • [42] Immunolocalization of keratan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate in periprosthetic breast capsules exhibiting synovial metaplasia
    Raso, DS
    Schulte, BA
    PLASTIC AND RECONSTRUCTIVE SURGERY, 1996, 98 (01) : 78 - 82
  • [43] Chondroitin sulfate in therapy osteoarthritis chronic pain patients according to actual clinical recommendations
    Shavlovskaya, Olga A.
    TERAPEVTICHESKII ARKHIV, 2021, 93 (12) : 1551 - 1555
  • [44] New clinical protocol to study patients with knee osteoarthritis and psoriasis treated with chondroitin sulfate
    Perez, M.
    Dalmau, J.
    Roe, E.
    Moller, L.
    Moragues, C.
    Marti, N.
    Benito, P.
    Monfort, J.
    Segales, N.
    Coll, M.
    Cuevas, J.
    Perna, C.
    Herrero, M.
    Montell, E.
    Verges, J.
    EADV: PROCEEDINGS OF THE 15TH CONGRESS OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2006, : 749 - +
  • [45] Sulfation pattern of chondroitin sulfate in human osteoarthritis cartilages reveals a lower level of chondroitin-4-sulfate
    Lin, Tzung-Sheng
    Hsieh, Chang-Hsun
    Kuo, Chin
    Juang, Yu-Pu
    Hsieh, Yves S. Y.
    Chiang, Hongsen
    Hung, Shang-Cheng
    Jiang, Ching-Chuan
    Liang, Pi-Hui
    CARBOHYDRATE POLYMERS, 2020, 229
  • [46] Raised chondroitin sulfate epitopes and hyaluronan in serum from rheumatoid arthritis and osteoarthritis patients
    Pothacharoen, P
    Teekachunhatean, S
    Louthrenoo, W
    Yingsung, W
    Ong-Chai, S
    Hardingham, T
    Kongtawelert, P
    OSTEOARTHRITIS AND CARTILAGE, 2006, 14 (03) : 299 - 301
  • [47] THE BENEFICIAL EFFECTS OF PHARMACEUTICAL-GRADE CHONDROITIN SULFATE ON CARDIOVASCULAR SYSTEM IN PATIENTS WITH OSTEOARTHRITIS
    De Abajo, F.
    Rodriguez-Martin, S.
    Barreira-Hernandez, D.
    Mazzuchelli, R.
    Martinez, N.
    Verges, J.
    AGING CLINICAL AND EXPERIMENTAL RESEARCH, 2023, 35 : S37 - S38
  • [48] LEVELS OF KERATAN SULFATE IN THE SERUM AND SYNOVIAL-FLUID OF PATIENTS WITH OSTEOARTHRITIS OF THE KNEE
    CAMPION, GV
    MCCRAE, F
    SCHNITZER, TJ
    LENZ, ME
    DIEPPE, PA
    THONAR, EJMA
    ARTHRITIS AND RHEUMATISM, 1991, 34 (10): : 1254 - 1259
  • [49] Characterization of Synovial Fluid Components: Albumin-Chondroitin Sulfate Interactions Seen through Molecular Dynamics
    Kruszewska, Natalia
    Mazurkiewicz, Adam
    Szala, Grzegorz
    Slomion, Malgorzata
    MATERIALS, 2022, 15 (19)
  • [50] Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis
    Henrotin, Yves
    Pesesse, Laurence
    Lambert, Cecile
    THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASE, 2014, 6 (01) : 20 - 34