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Soluble P selectin in synovial fluid level is correlated with the radiographic severity of knee osteoarthritis
Clinica Chimica Acta 411 (2010) 1529–1531
Contents lists available at ScienceDirect
Clinica Chimica Acta j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / c l i n c h i m
Short communication
Soluble P selectin in synovial fluid level is correlated with the radiographic severity of knee osteoarthritis Tao Cheng, Feng-Feng Li, Song Zhao, Xiao-Chun Peng, Xian-Long Zhang ⁎ a
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, People's Republic of China
a r t i c l e
i n f o
Article history: Received 2 March 2010 Received in revised form 5 May 2010 Accepted 6 May 2010 Available online 1 June 2010 Keyword: Osteoarthritis P selectin Biomarker C-reactive protein
a b s t r a c t Background: Recent studies provide evidence that inflammation is a feature of the disease process in Osteoarthritis (OA). The clinical significance of P selectin (Ps) in OA has not been adequately studied and the association between Ps level and OA severity remains unknown. Methods: We enrolled 120 knee OA subjects and 45 controls. All patients were scored for Kellgren–Lawrence grade (0–4). The Ps in serum and synovial fluid (SF) as well as serum C-reactive protein (CRP) levels were detected. Results: The mean Ps level in OA subjects was markedly increased than that in controls. In OA patients, the SF Ps levels increased with the severity of KL scores and significantly correlated with severity of disease (r = 0.546, P b 0.001) and serum CRP level (r = 0.488, P b 0.001). However, the serum Ps level did not show a significant correlation with the severity of OA. Conclusion: The Ps levels in SF were significantly correlated with the severity of OA, suggesting that it may be used as a biomarker to evaluate the progression of OA. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Osteoarthritis (OA) is generally considered as a degenerative, noninflammatory disease. However, recent studies showed that prominent pro-inflammatory mediators are involved in the disease pathogenesis of OA, suggesting that OA is also a chronic inflammatory process [1–3]. Increased systematic inflammation marker in the plasma of OA patients has been associated with the radiographic severity in patients with hand, knee or hip OA [4–8]. Adhesion molecules play an important role in the chronic inflammatory response. P selectin (Ps), a member of the selectin family of adhesion molecules, mediates the rolling and adhesion between the endothelial cells and the neutrophils. Inhibition or losses of Ps function result in a marked reduction of leukocyte rolling and emigration and inhibits the inflammation reaction [9,10]. The role of Ps in the leukocyte accumulation and migration in arthritis animal models were previously reported. In adjuvantinduced arthritis rat model, anti-Ps antibody significantly reduced
Abbreviations: OA, Osteoarthritis; RA, Rheumatoid arthritis; SF, Synovial fluid; hsCRP, High sensitivity C-reactive protein; Ps, P selectin; KL grade, Kellgren–Lawrence grade; ELISA, Enzyme-linked immunosorbent assay; BMI, Body mass index; IL-1, Interleukin-1; TNF α, Tumor necrosis factor α. ⁎ Corresponding author. Tel.: + 86 21 64369181; fax: + 86 21 64701361. E-mail address: [email protected] (X.-L. Zhang). 0009-8981/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2010.05.009
accumulation of monocytes and neutrophils joints [11]. In the murine collagen-immunized arthritis model, Ps deficiency resulted in accelerated onset and development of arthritis [12]. Furthermore, plasma soluble Ps level was suggested as biomarker to evaluate the disease progression of arthritis [13–16].
2. Methods 2.1. Study population We enrolled 120 knee OA subjects in this study. All patients met clinical symptomatic criteria (American College of Rheumatology) and radiographic criteria for OA of at least one knee. The age range was 40 to 65 y and the mean age was 48.5 y. All patients underwent standardized fixed-flexion posteroanterior knee radiographs with a positioning frame. Radiographs were scored for Kellgren–Lawrence grade (0–4), medial and lateral joint space width (JSW) at the midportion of the joint space via electronic calipers [17]. Radiographic KL scores were determined by a blinded, experienced musculoskeletal radiologist. Exclusion criteria were histories of corticosteroids, bilateral knee replacements, other forms of arthritis, cancer, or other chronic diseases. We also enrolled 45 sex and age matched subjects with normal knee radiographs as controls. The fasting blood was obtained from both cases and controls. The synovial fluids (SF) were obtained from all cases, but not from controls for ethical reasons.
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T. Cheng et al. / Clinica Chimica Acta 411 (2010) 1529–1531
Clinical characteristics e.g. sex, age, body mass index (BMI), smoking status, diabetes mellitus (DM) were collected from cases and controls. 2.2. P selectin and hsCRP detection Collected blood serum and synovial fluid were obtained and stored. An hsCRP enzyme-linked immunosorbent assay (ELISA) kit was utilized with a lower-limit of detection of 0.5 mg/l. Ps in the serum and synovial fluid was analyzed by a ELISA technique using monoclonal antibodies. Samples were assayed in duplicate according to the manufacturer's suggested procedures. 2.3. Statistical analysis All values were presented as mean and SD. Student's t and χ2 test were used to evaluate significance in clinical characteristics between the two groups. Statistical significance of the correlation was determined by Spearman's coefficient and a multinoninal logistic regression analyses. A P b 0.05 was considered significant. All statistical analysis was performed with SPSS for windows 16.0. 3. Results There were no significant differences in age and sex distribution as well as percentage of smokers and DM between OA subjects and controls (Table 1). The mean BMI in OA group is slightly higher than that in controls (P = 0.058). The mean hsCRP level in OA subjects was significantly higher than that in controls (P = 0.017), whereas no significant difference in the mean serum Ps level was noted between OA subjects and controls (P = 0.063). Fig. 1 summarized the Ps levels in SF according to KL grading in OA subjects. The mean Ps levels in SF increased with the severity of KL scores. Patients with KL grade 3 and 4 had significantly higher SF Ps levels than those with KL grade 1 and 2 (P b 0.05). No significant differences in the serum Ps levels were noted among OA subjects with KL 1, 2, 3 and 4 grades (data not shown). Fig. 2 showed the serum hsCRP levels according to the KL grading. A marked elevation of mean hsCRP level was observed in patients with KL3 and 4 than patients with KL13 and 2. By Spearman analyses, we found that both the SF Ps levels were significantly correlated with the severity of OA disease (r = 0.546, P b 0.001). As BIM, age and sex can influence the severity of OA, we further performed a multinomial logistic regression analyses to evaluate the association between SF Ps levels and OA severity by taking BMI, age and sex as covariates. There was still a positive association between SF Ps levels and the severity of OA disease after controlling of the influence of BMI, age and sex (df = 97, P = 0.016). The serum hsCRP levels were correlated to the OA severity as well (r = 0.488, P b 0.001). However, no correlation was found between the serum Ps levels and the OA severity (r = 0.267, P = 0.062). Fig. 3 showed the correlation between the Ps levels in SF and the serum hsCRP(r = 0.466, P b 0.01). No positive correlation was observed between the Ps levels in serum and SF (r = 0.367, P = 0.079). No positive correlation between the SF Ps levels and BMI was observed (r = 0.162, P = 0.073).
Fig. 1. Ps levels in SF according to the radiographic severity by KL grading.
4. Discussion In this study, we investigated the association between the Ps levels in serum and SF with the radiographic severity of OA. We found that the Ps levels in SF were closely related with the severity of OA and serum hsCRP levels, suggesting that Ps in SF may be a biomarker to evaluate the progression of OA. Recent studies provide evidence that inflammation is a feature of the disease process in OA at both its early and end stage [18,19]. Histological analysis of synovial biopsies confirmed mild to moderate synovial inflammation in more than one third of patients with OA [20,21]. A systematic inflammation marker, serum CRP is proposed as a biomarker for OA progression. [22,23]. So far, the clinical significance of Ps in OA has not been adequately studied. The soluble serum Ps levels were less increased in OA patients than in RA and Psoriatic arthritis patients. [14,16], but no study regarding the association between Ps level and OA severity has been reported. In present study, we found the Ps levels in SF increased with the radiographic severity of OA assessed by KL scores. The Ps levels in SF and serum hsCRP levels were significantly correlated with the graphic severity of OA. A positive correlation exists between the SF Ps levels and the serum hsCRP levels. Our results suggest that SF Ps may be an alternative biomarker associated with radiographic severity of OA. Inflammatory mediators regulate breakdown of collagen, proteoglycans, and bone that constitute the articular joint tissues and appear to be part of the destructive process in OA [24–26]. Several cytokines, e.g. interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), have been implicated in the dys-regulation of bone and cartilage remodeling
Table 1 Clinical characteristics between OA subjects and controls.
Age (years) Sex (male/female) BMI (m/kg2) Smoker (%) DM (%) hsCRP (mg/L) Serum Ps (ng/L)
OA subjects
Controls
P
45.6 ± 8.8 56/44 27.3 ± 3.9 53.5 37.4 3.12 ± 0.83 115.4 ± 45.6
46.2 ± 7.4 23/21 25.8 ± 3.2 54.3 38.6 1.01 ± 0.37 113.2 ± 42.5
NS NS 0.057 NS NS 0.017 0.063
Fig. 2. hsCRP levels in serum according to according to the radiographic severity by KL grading.
T. Cheng et al. / Clinica Chimica Acta 411 (2010) 1529–1531
Fig. 3. Correlation between Ps levels in SF and the serum hsCRP level.
characteristic of RA and/or OA. As Ps expression on endothelial cells can be unregulated by TNF-α and IL-1, we suggest that the increased Ps levels in SF be a result of accelerated joint damaged caused by local inflammation [27,28]. In conclusion, we found that the Ps level from SF might be a biomarker to evaluate the radiographic severity in knee OA patients. As this is a small-size study, this conclusion needs to be testified in a larger scale study. Acknowledgements We thank Dr. Han Yang for his help in statistical analysis and thank Dr. Xianguo Ma for his contribution to sample collection and processing. This work was supported by grants from the Doctoral Students Innovation Fund of Shanghai Jiao Tong University School of Medicine (BXJ0930) and New Medical Technology Development Program of Shanghai Shenkang Hospital Development Center (SHDC12006103). References [1] Li X, Ellman M, Muddasani P, et al. Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis. Arthritis Rheum 2009;60:513–23. [2] Hussain SA, Jassim NA, Numan IT, Al II K, Abdullah TA. Anti-inflammatory activity of silymarin in patients with knee osteoarthritis. A comparative study with piroxicam and meloxicam. Saudi Med J 2009;30:98–103. [3] Meini S, Maggi CA. Knee osteoarthritis: a role for bradykinin? Inflamm Res 2008;57:351–61. [4] Wolfe F. The C-reactive protein but not erythrocyte sedimentation rate is associated with clinical severity in patients with osteoarthritis of the knee or hip. J Rheumatol 1997;24:1486–8.
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[5] Conrozier T, Carlier MC, Mathieu P, et al. Serum levels of YKL-40 and C reactive protein in patients with hip osteoarthritis and healthy subjects: a cross sectional study. Ann Rheum Dis 2000;59:828–31. [6] Engstrom G, Gerhardsson de Verdier M, Rollof J, Nilsson PM, Lohmander LS. C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study. Osteoarthr Cartil 2009;17:168–73. [7] Punzi L, Ramonda R, Oliviero F, et al. Value of C reactive protein in the assessment of erosive osteoarthritis of the hand. Ann Rheum Dis 2005;64:955–7. [8] Hurter K, Spreng D, Rytz U, Schawalder P, Ott-Knusel F, Schmokel H. Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis. Vet J 2005;169:281–5. [9] Rossi B, Constantin G. Anti-selectin therapy for the treatment of inflammatory diseases. Inflamm Allergy Drug Targets 2008;7:85–93. [10] Wang HB, Wang JT, Zhang L, et al. P-selectin primes leukocyte integrin activation during inflammation. Nat Immunol 2007;8:882–92. [11] Walter UM, Issekutz AC. The role of E- and P-selectin in neutrophil and monocyte migration in adjuvant-induced arthritis in the rat. Eur J Immunol 1997;27:1498–505. [12] Ruth JH, Amin MA, Woods JM, et al. Accelerated development of arthritis in mice lacking endothelial selectins. Arthritis Res Ther 2005;7:R959–70. [13] De Benedetti F, Vivarelli M, Pignatti P, et al. Circulating levels of soluble E-selectin, Pselectin and intercellular adhesion molecule-1 in patients with juvenile idiopathic arthritis. J Rheumatol 2000;27:2246–50. [14] Scrivo R, Spadaro A, Riccieri V, et al. Soluble P-selectin levels in synovial fluid and serum from patients with psoriatic arthritis. Reumatismo 2005;57:250–5. [15] Veale DJ, Maple C, Kirk G, McLaren M, Belch JJ. Soluble cell adhesion molecules—Pselectin and ICAM-1, and disease activity in patients receiving sulphasalazine for active rheumatoid arthritis. Scand J Rheumatol 1998;27:296–9. [16] Hosaka S, Shah MR, Pope RM, Koch AE. Soluble forms of P-selectin and intercellular adhesion molecule-3 in synovial fluids. Clin Immunol Immunopathol 1996;78:276–82. [17] Clarke GR, Willis LA, Fish WW, Nichols PJ. A radiological assessment of osteoarthrosis of the knee: experiments in observer error. Rheumatol Rehabil 1975;14:81–6. [18] Saxne T, Lindell M, Mansson B, Petersson IF, Heinegard D. Inflammation is a feature of the disease process in early knee joint osteoarthritis. Rheumatol (Oxf) 2003;42:903–4. [19] Appelboom T, Emery P, Tant L, Dumarey N, Schoutens A. Evaluation of technetium-99m-ciprofloxacin (Infecton) for detecting sites of inflammation in arthritis. Rheumatol (Oxf) 2003;42:1179–82. [20] Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol 1997;24:365–71. [21] Baddour VT, Bradley JD. Clinical assessment and significance of inflammation in knee osteoarthritis. Curr Rheumatol Rep 1999;1:59–63. [22] Spector TD, Hart DJ, Nandra D, et al. Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 1997;40:723–7. [23] Sturmer T, Brenner H, Koenig W, Gunther KP. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis 2004;63:200–5. [24] Neidhart M, Gay RE, Gay S. Anti-interleukin-1 and anti-CD44 interventions producing significant inhibition of cartilage destruction in an in vitro model of cartilage invasion by rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 2000;43:1719–28. [25] Davies ME, Dingle JT, Pigott R, Power C, Sharma H. Expression of intercellular adhesion molecule 1 (ICAM-1) on human articular cartilage chondrocytes. Connect Tissue Res 1991;26:207–16. [26] Schett G, Kiechl S, Bonora E, et al. Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints. Arthritis Rheum 2009;60: 2381–9. [27] Tremblay C, Paradis M, Dore M. Expression of E- and P-selectin in tumor necrosis factor-induced dermatitis in dogs. Vet Pathol 2001;38:261–8. [28] Gotsch U, Jager U, Dominis M, Vestweber D. Expression of P-selectin on endothelial cells is upregulated by LPS and TNF-alpha in vivo. Cell Adhes Commun 1994;2:7–14.
Contents lists available at ScienceDirect
Clinica Chimica Acta j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / c l i n c h i m
Short communication
Soluble P selectin in synovial fluid level is correlated with the radiographic severity of knee osteoarthritis Tao Cheng, Feng-Feng Li, Song Zhao, Xiao-Chun Peng, Xian-Long Zhang ⁎ a
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, People's Republic of China
a r t i c l e
i n f o
Article history: Received 2 March 2010 Received in revised form 5 May 2010 Accepted 6 May 2010 Available online 1 June 2010 Keyword: Osteoarthritis P selectin Biomarker C-reactive protein
a b s t r a c t Background: Recent studies provide evidence that inflammation is a feature of the disease process in Osteoarthritis (OA). The clinical significance of P selectin (Ps) in OA has not been adequately studied and the association between Ps level and OA severity remains unknown. Methods: We enrolled 120 knee OA subjects and 45 controls. All patients were scored for Kellgren–Lawrence grade (0–4). The Ps in serum and synovial fluid (SF) as well as serum C-reactive protein (CRP) levels were detected. Results: The mean Ps level in OA subjects was markedly increased than that in controls. In OA patients, the SF Ps levels increased with the severity of KL scores and significantly correlated with severity of disease (r = 0.546, P b 0.001) and serum CRP level (r = 0.488, P b 0.001). However, the serum Ps level did not show a significant correlation with the severity of OA. Conclusion: The Ps levels in SF were significantly correlated with the severity of OA, suggesting that it may be used as a biomarker to evaluate the progression of OA. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Osteoarthritis (OA) is generally considered as a degenerative, noninflammatory disease. However, recent studies showed that prominent pro-inflammatory mediators are involved in the disease pathogenesis of OA, suggesting that OA is also a chronic inflammatory process [1–3]. Increased systematic inflammation marker in the plasma of OA patients has been associated with the radiographic severity in patients with hand, knee or hip OA [4–8]. Adhesion molecules play an important role in the chronic inflammatory response. P selectin (Ps), a member of the selectin family of adhesion molecules, mediates the rolling and adhesion between the endothelial cells and the neutrophils. Inhibition or losses of Ps function result in a marked reduction of leukocyte rolling and emigration and inhibits the inflammation reaction [9,10]. The role of Ps in the leukocyte accumulation and migration in arthritis animal models were previously reported. In adjuvantinduced arthritis rat model, anti-Ps antibody significantly reduced
Abbreviations: OA, Osteoarthritis; RA, Rheumatoid arthritis; SF, Synovial fluid; hsCRP, High sensitivity C-reactive protein; Ps, P selectin; KL grade, Kellgren–Lawrence grade; ELISA, Enzyme-linked immunosorbent assay; BMI, Body mass index; IL-1, Interleukin-1; TNF α, Tumor necrosis factor α. ⁎ Corresponding author. Tel.: + 86 21 64369181; fax: + 86 21 64701361. E-mail address: [email protected] (X.-L. Zhang). 0009-8981/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2010.05.009
accumulation of monocytes and neutrophils joints [11]. In the murine collagen-immunized arthritis model, Ps deficiency resulted in accelerated onset and development of arthritis [12]. Furthermore, plasma soluble Ps level was suggested as biomarker to evaluate the disease progression of arthritis [13–16].
2. Methods 2.1. Study population We enrolled 120 knee OA subjects in this study. All patients met clinical symptomatic criteria (American College of Rheumatology) and radiographic criteria for OA of at least one knee. The age range was 40 to 65 y and the mean age was 48.5 y. All patients underwent standardized fixed-flexion posteroanterior knee radiographs with a positioning frame. Radiographs were scored for Kellgren–Lawrence grade (0–4), medial and lateral joint space width (JSW) at the midportion of the joint space via electronic calipers [17]. Radiographic KL scores were determined by a blinded, experienced musculoskeletal radiologist. Exclusion criteria were histories of corticosteroids, bilateral knee replacements, other forms of arthritis, cancer, or other chronic diseases. We also enrolled 45 sex and age matched subjects with normal knee radiographs as controls. The fasting blood was obtained from both cases and controls. The synovial fluids (SF) were obtained from all cases, but not from controls for ethical reasons.
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T. Cheng et al. / Clinica Chimica Acta 411 (2010) 1529–1531
Clinical characteristics e.g. sex, age, body mass index (BMI), smoking status, diabetes mellitus (DM) were collected from cases and controls. 2.2. P selectin and hsCRP detection Collected blood serum and synovial fluid were obtained and stored. An hsCRP enzyme-linked immunosorbent assay (ELISA) kit was utilized with a lower-limit of detection of 0.5 mg/l. Ps in the serum and synovial fluid was analyzed by a ELISA technique using monoclonal antibodies. Samples were assayed in duplicate according to the manufacturer's suggested procedures. 2.3. Statistical analysis All values were presented as mean and SD. Student's t and χ2 test were used to evaluate significance in clinical characteristics between the two groups. Statistical significance of the correlation was determined by Spearman's coefficient and a multinoninal logistic regression analyses. A P b 0.05 was considered significant. All statistical analysis was performed with SPSS for windows 16.0. 3. Results There were no significant differences in age and sex distribution as well as percentage of smokers and DM between OA subjects and controls (Table 1). The mean BMI in OA group is slightly higher than that in controls (P = 0.058). The mean hsCRP level in OA subjects was significantly higher than that in controls (P = 0.017), whereas no significant difference in the mean serum Ps level was noted between OA subjects and controls (P = 0.063). Fig. 1 summarized the Ps levels in SF according to KL grading in OA subjects. The mean Ps levels in SF increased with the severity of KL scores. Patients with KL grade 3 and 4 had significantly higher SF Ps levels than those with KL grade 1 and 2 (P b 0.05). No significant differences in the serum Ps levels were noted among OA subjects with KL 1, 2, 3 and 4 grades (data not shown). Fig. 2 showed the serum hsCRP levels according to the KL grading. A marked elevation of mean hsCRP level was observed in patients with KL3 and 4 than patients with KL13 and 2. By Spearman analyses, we found that both the SF Ps levels were significantly correlated with the severity of OA disease (r = 0.546, P b 0.001). As BIM, age and sex can influence the severity of OA, we further performed a multinomial logistic regression analyses to evaluate the association between SF Ps levels and OA severity by taking BMI, age and sex as covariates. There was still a positive association between SF Ps levels and the severity of OA disease after controlling of the influence of BMI, age and sex (df = 97, P = 0.016). The serum hsCRP levels were correlated to the OA severity as well (r = 0.488, P b 0.001). However, no correlation was found between the serum Ps levels and the OA severity (r = 0.267, P = 0.062). Fig. 3 showed the correlation between the Ps levels in SF and the serum hsCRP(r = 0.466, P b 0.01). No positive correlation was observed between the Ps levels in serum and SF (r = 0.367, P = 0.079). No positive correlation between the SF Ps levels and BMI was observed (r = 0.162, P = 0.073).
Fig. 1. Ps levels in SF according to the radiographic severity by KL grading.
4. Discussion In this study, we investigated the association between the Ps levels in serum and SF with the radiographic severity of OA. We found that the Ps levels in SF were closely related with the severity of OA and serum hsCRP levels, suggesting that Ps in SF may be a biomarker to evaluate the progression of OA. Recent studies provide evidence that inflammation is a feature of the disease process in OA at both its early and end stage [18,19]. Histological analysis of synovial biopsies confirmed mild to moderate synovial inflammation in more than one third of patients with OA [20,21]. A systematic inflammation marker, serum CRP is proposed as a biomarker for OA progression. [22,23]. So far, the clinical significance of Ps in OA has not been adequately studied. The soluble serum Ps levels were less increased in OA patients than in RA and Psoriatic arthritis patients. [14,16], but no study regarding the association between Ps level and OA severity has been reported. In present study, we found the Ps levels in SF increased with the radiographic severity of OA assessed by KL scores. The Ps levels in SF and serum hsCRP levels were significantly correlated with the graphic severity of OA. A positive correlation exists between the SF Ps levels and the serum hsCRP levels. Our results suggest that SF Ps may be an alternative biomarker associated with radiographic severity of OA. Inflammatory mediators regulate breakdown of collagen, proteoglycans, and bone that constitute the articular joint tissues and appear to be part of the destructive process in OA [24–26]. Several cytokines, e.g. interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), have been implicated in the dys-regulation of bone and cartilage remodeling
Table 1 Clinical characteristics between OA subjects and controls.
Age (years) Sex (male/female) BMI (m/kg2) Smoker (%) DM (%) hsCRP (mg/L) Serum Ps (ng/L)
OA subjects
Controls
P
45.6 ± 8.8 56/44 27.3 ± 3.9 53.5 37.4 3.12 ± 0.83 115.4 ± 45.6
46.2 ± 7.4 23/21 25.8 ± 3.2 54.3 38.6 1.01 ± 0.37 113.2 ± 42.5
NS NS 0.057 NS NS 0.017 0.063
Fig. 2. hsCRP levels in serum according to according to the radiographic severity by KL grading.
T. Cheng et al. / Clinica Chimica Acta 411 (2010) 1529–1531
Fig. 3. Correlation between Ps levels in SF and the serum hsCRP level.
characteristic of RA and/or OA. As Ps expression on endothelial cells can be unregulated by TNF-α and IL-1, we suggest that the increased Ps levels in SF be a result of accelerated joint damaged caused by local inflammation [27,28]. In conclusion, we found that the Ps level from SF might be a biomarker to evaluate the radiographic severity in knee OA patients. As this is a small-size study, this conclusion needs to be testified in a larger scale study. Acknowledgements We thank Dr. Han Yang for his help in statistical analysis and thank Dr. Xianguo Ma for his contribution to sample collection and processing. This work was supported by grants from the Doctoral Students Innovation Fund of Shanghai Jiao Tong University School of Medicine (BXJ0930) and New Medical Technology Development Program of Shanghai Shenkang Hospital Development Center (SHDC12006103). References [1] Li X, Ellman M, Muddasani P, et al. Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis. Arthritis Rheum 2009;60:513–23. [2] Hussain SA, Jassim NA, Numan IT, Al II K, Abdullah TA. Anti-inflammatory activity of silymarin in patients with knee osteoarthritis. A comparative study with piroxicam and meloxicam. Saudi Med J 2009;30:98–103. [3] Meini S, Maggi CA. Knee osteoarthritis: a role for bradykinin? Inflamm Res 2008;57:351–61. [4] Wolfe F. The C-reactive protein but not erythrocyte sedimentation rate is associated with clinical severity in patients with osteoarthritis of the knee or hip. J Rheumatol 1997;24:1486–8.
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[5] Conrozier T, Carlier MC, Mathieu P, et al. Serum levels of YKL-40 and C reactive protein in patients with hip osteoarthritis and healthy subjects: a cross sectional study. Ann Rheum Dis 2000;59:828–31. [6] Engstrom G, Gerhardsson de Verdier M, Rollof J, Nilsson PM, Lohmander LS. C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study. Osteoarthr Cartil 2009;17:168–73. [7] Punzi L, Ramonda R, Oliviero F, et al. Value of C reactive protein in the assessment of erosive osteoarthritis of the hand. Ann Rheum Dis 2005;64:955–7. [8] Hurter K, Spreng D, Rytz U, Schawalder P, Ott-Knusel F, Schmokel H. Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis. Vet J 2005;169:281–5. [9] Rossi B, Constantin G. Anti-selectin therapy for the treatment of inflammatory diseases. Inflamm Allergy Drug Targets 2008;7:85–93. [10] Wang HB, Wang JT, Zhang L, et al. P-selectin primes leukocyte integrin activation during inflammation. Nat Immunol 2007;8:882–92. [11] Walter UM, Issekutz AC. The role of E- and P-selectin in neutrophil and monocyte migration in adjuvant-induced arthritis in the rat. Eur J Immunol 1997;27:1498–505. [12] Ruth JH, Amin MA, Woods JM, et al. Accelerated development of arthritis in mice lacking endothelial selectins. Arthritis Res Ther 2005;7:R959–70. [13] De Benedetti F, Vivarelli M, Pignatti P, et al. Circulating levels of soluble E-selectin, Pselectin and intercellular adhesion molecule-1 in patients with juvenile idiopathic arthritis. J Rheumatol 2000;27:2246–50. [14] Scrivo R, Spadaro A, Riccieri V, et al. Soluble P-selectin levels in synovial fluid and serum from patients with psoriatic arthritis. Reumatismo 2005;57:250–5. [15] Veale DJ, Maple C, Kirk G, McLaren M, Belch JJ. Soluble cell adhesion molecules—Pselectin and ICAM-1, and disease activity in patients receiving sulphasalazine for active rheumatoid arthritis. Scand J Rheumatol 1998;27:296–9. [16] Hosaka S, Shah MR, Pope RM, Koch AE. Soluble forms of P-selectin and intercellular adhesion molecule-3 in synovial fluids. Clin Immunol Immunopathol 1996;78:276–82. [17] Clarke GR, Willis LA, Fish WW, Nichols PJ. A radiological assessment of osteoarthrosis of the knee: experiments in observer error. Rheumatol Rehabil 1975;14:81–6. [18] Saxne T, Lindell M, Mansson B, Petersson IF, Heinegard D. Inflammation is a feature of the disease process in early knee joint osteoarthritis. Rheumatol (Oxf) 2003;42:903–4. [19] Appelboom T, Emery P, Tant L, Dumarey N, Schoutens A. Evaluation of technetium-99m-ciprofloxacin (Infecton) for detecting sites of inflammation in arthritis. Rheumatol (Oxf) 2003;42:1179–82. [20] Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol 1997;24:365–71. [21] Baddour VT, Bradley JD. Clinical assessment and significance of inflammation in knee osteoarthritis. Curr Rheumatol Rep 1999;1:59–63. [22] Spector TD, Hart DJ, Nandra D, et al. Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 1997;40:723–7. [23] Sturmer T, Brenner H, Koenig W, Gunther KP. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis 2004;63:200–5. [24] Neidhart M, Gay RE, Gay S. Anti-interleukin-1 and anti-CD44 interventions producing significant inhibition of cartilage destruction in an in vitro model of cartilage invasion by rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 2000;43:1719–28. [25] Davies ME, Dingle JT, Pigott R, Power C, Sharma H. Expression of intercellular adhesion molecule 1 (ICAM-1) on human articular cartilage chondrocytes. Connect Tissue Res 1991;26:207–16. [26] Schett G, Kiechl S, Bonora E, et al. Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints. Arthritis Rheum 2009;60: 2381–9. [27] Tremblay C, Paradis M, Dore M. Expression of E- and P-selectin in tumor necrosis factor-induced dermatitis in dogs. Vet Pathol 2001;38:261–8. [28] Gotsch U, Jager U, Dominis M, Vestweber D. Expression of P-selectin on endothelial cells is upregulated by LPS and TNF-alpha in vivo. Cell Adhes Commun 1994;2:7–14.