Abstract
Introduction: Osteoarthritis (OA) is the commonest joint disease and is thought to be caused by an imbalance between synthesis and degradation of extracellular cartilage/bone matrix proteins. An overproduction of cartilage-degrading mediators from the inflamed synovial membrane (SM) is now attracting interest. To date, direct in vivo imaging of human SM microcirculation is impossible. The relationship between OA-induced SM microcirculatory disturbances and OA-disease-severity is unknown. Methods: 20 patients with OA of the knee were investigated during total knee arthroplasty by 1)orthogonal polarization spectral (OPS-)imaging of the SM, 2)growth factor synovial fluid (SF) analysis and 3)histological grading of SM inflammation. Disease-specific measure of pain, stiffness and function (WOMAC-Scores) and radiographic stage of disease (Ahlbaeck-score) were assessed in all patients. In vivo OPS-imaging of the SM was performed in 6-10 regions. SF was transcapsularily aspirated for ELISA-analysis of VEGF, MMP1+3, TIMP2, PGE2. SM biopsies were harvested for histolog. graduation of synovialitis. Results: Radiographics in OA-knees revealed 0,3,10,5, and 2 patients for Ahlbaeck-stage 1,2,3,4, and 5. WOMAC score was 5.9 ± 1.4 (pain), 5.6 ± 1.8 (stiffness) and 5.8 ± 1.2 (function). OPS-imaging allowed to visualize human SM microcirculation with funct. capill. density (FCD:190.1 ± 34.0 cm−1), capillary/venular diameters (D: 9.1 ± 2.2/31.5 ± 27.2µm), capillary/ venular RBCV (276 ± 191/190 ± 103µm/s), VBF (17 ± 14/111 ± 105pl/s). Synovialitis score was 2.8 ± 1.1. Synovial levels (pg/ml) were increased with VEGF(1321,3 ± 868,3), MMP-1(20,4 ± 19,3) and -3(1719,8 ± 1646,2), TIMP-2(396,5 ± 86,1), PGE-2(571,3 ± 331,0). Regression of patient age on synovialitis score revealed an association (R = 0.67). There was an inverse correlation between RBCV and VBF in capillaries/venules and the WOMAC-pain score (R = −0.56,R = −0.64). Venular VBF correlated to synovial PGE2-levels. Radiographic Ahlbaeck-stage showed a relation to the VEGF-level (R = 0.76). Elevated TIMP-2-level was associated with increased venular D (R = 0.6) and VBF (R = 0.55). MMP-1-levels significantly correlated to WOMAC-pain score (R = 0.6). Conclusion: This study presents for the first time direct in vivo visualization and quantification of the SM microcirculation in OA patients. The correlations of 1)increased VEGF-levels with radiographic damage, 2)venular D and reduced VBF with pain, 3)synovial blood flow and PGE2 levels and 4) MMP-1 and WOMAC-pain score reflect a causative role of SM microcirculatory disturbances, angiogenic factors in perpetuation of OA-synovitis. These interactions may have therapeutic implications in view of protecting SM microcirculation and targeting expression of destructive mediators in order counteract OA progression.
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© 2008 Springer Medizin Verlag Heidelberg
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Schaser, KD. et al. (2008). In vivo Analyse der humanen synovialen Mikrozirkulation bei Gonarthrose: Interaktion von Mikrozirkulationsstörung, Matrixdegradation und Arthroseprogression. In: Arbogast, R., Schackert, H.K., Bauer, H. (eds) Chirurgisches Forum 2008. Deutsche Gesellschaft für Chirurgie, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78833-1_6
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DOI: https://doi.org/10.1007/978-3-540-78833-1_6
Publisher Name: Springer, Berlin, Heidelberg
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