Osteopontin and adiponectin: how far are they related in the complexity of psoriasis?
- 302 Downloads
Increasing attention has been drawn towards the involvement of both osteopontin (OPN) and adiponectin in psoriasis. The relationship between them has been studied before in the context of essential hypertension. To our knowledge, whether a relation between them exists in cases of psoriasis and the metabolic status in such patients have not been investigated. We aimed to verify their possible roles and relations in psoriasis and its metabolic associations. 35 patients with psoriasis vulgaris and 35 controls were included. Patients were clinically assessed by PASI and investigated for the presence of metabolic syndrome (MetS) and/or its components. Plasma levels of OPN and adiponectin were measured using ELISA. On comparing psoriatics to controls, patients showed significantly elevated levels of OPN (90.474 ± 21.22 vs 34.709 ± 13.95 ng/mL) and significantly depressed levels of adiponectin (4,586 ± 1.187 vs 5,905 ± 1.374 ng/mL), (p < 0.001). Strong negative correlation between plasma OPN and adiponectin was detected in patients (r = −0.912, p < 0.001), but not in controls. OPN elevation was related to diabetes mellitus, insulin resistance, and MetS. Adiponectin depression was related to body mass index, and MetS. This study demonstrates for the first time a significant correlation between OPN and adiponectin in psoriasis, hypothesized to be mostly attributed to the inflammatory milieu of psoriasis and MetS as well as the enhanced renin–angiotensin–aldosterone system previously documented in psoriasis. Adjuvant therapies aiming at modulating levels of OPN and adiponectin are speculated to add benefit in psoriasis treatment and protecting against its metabolic risks.
KeywordsAdiponectin Metabolic syndrome Osteopontin Psoriasis
Psoriasis is a chronic disease that affects 1–3 % of the population . Patients with psoriasis have a higher risk of cardiovascular and metabolic co-morbidities, attributable to lifestyle factors as well as to shared inflammatory pathways and genetic factors .
Osteopontin (OPN) is an acidic glycoprotein, expressed by many different cell types including activated immune cells such as macrophages, natural killer cells and activated T lymphocytes . OPN gene expression is extensively up-regulated upon obesity in adipose tissue, and plasma OPN concentrations are elevated in morbidly obese patients . Moreover, OPN notably plays a role in various inflammatory disorders, with increasing attention drawn towards its possible role in psoriasis [5, 6, 10, 17].
Adiponectin is an adipose tissue mass-dependent cytokine . Adiponectin has insulin-sensitizing and anti-inflammatory effects with diverse protective properties on the heart and blood vessels . Kaur et al.  stated that there is no particular pattern for adiponectin expression in psoriasis, as it could be reduced [30, 31], unchanged  or even increased [14, 18].
The relationship between OPN and adiponectin has been studied before in the context of essential hypertension . To our knowledge, whether a relation between them exists in cases of psoriasis and the metabolic status in such patients have not yet been investigated. This was the impetus behind the present study aiming to verify their possible roles and relations in psoriasis and its metabolic associations.
Patients and methods
Thirty-five patients (≥18 years of age) with psoriasis vulgaris attending the dermatology outpatient clinic of Kasr AlAini Hospital at Cairo University were recruited sequentially for this study. Patients have been in wash-out from topical and systemic medications, except for Vaseline for 4 weeks. Pregnant and lactating females were excluded from the study. Thirty-five age, gender and body mass index (BMI) matched healthy control subjects were also enrolled. Patients and healthy volunteers signed informed written consent forms to participate in this study, which has been approved by the institutional Research Ethics Committee (REC).
Diagnosis of psoriasis was made on clinical basis. The extent and severity of the disease were assessed using Psoriasis Area and Severity Index (PASI). Mild disease was considered when PASI was ≤10, whereas moderate and severe disease was considered when PASI was >10 .
A detailed history was retrieved from each participant and clinical parameters including PASI, body weight, height, BMI, waist circumference (WC) and blood pressure readings were determined. Serum lipids, blood glucose levels, homeostasis model assessment for insulin resistance (HOMA-IR) and presence of metabolic syndrome (MetS) were assessed in both groups.
Raised triglycerides (TG) level: ≥1.7 mmol/L (150 mg/dL).
Reduced high-density lipoprotein (HDL), cholesterol <1.03 mmol/L (40 mg/dL) in males and <1.29 mmol/L (50 mg/dL) in females.
Raised blood pressure (systolic ≥130 or diastolic ≥85 mmHg).
Raised fasting plasma glucose ≥5.6 mmol/L (100 mg/dL).
After overnight fasting, 5 ml venous blood samples were collected from patients and controls. Plasma OPN and adiponectin were examined using enzyme linked immunosorbent assay (ELISA) (Quantikine R&D system, Inc., Minneapolis, MN, USA), (Human Adiponectin; Quantikine R&D Systems, Minneapolis, MN, USA). Enzymatic colorimetric methods were adopted to evaluate the fasting blood glucose (glucose oxidase method), plasma cholesterol, triglycerides and high-density lipoprotein (HDL) levels. IR was calculated through homeostasis model assessment for insulin resistance (HOMA-IR).
Data were statistically described in terms of mean ± standard deviation (±SD), or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables between the study groups was done using Student t test for independent samples in comparing two groups when normally distributed and Mann–Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi-square (χ2) test was performed. Exact test was used instead when the expected frequency is less than 5. p values less than 0.05 were considered statistically significant. Correlations were done using Pearson Moment correlation equation when data were normally distributed, while non-normal data were correlated using Spearman correlation equation. Multivariate stepwise regression analyses were done to determine the independent effectors for plasma OPN and adiponectin levels. The following clinical parameters: presence of psoriasis, BMI, WC, presence of MetS, DM, IR, HTN and dyslipidaemia were enrolled in the model. All statistical calculations were done using computer programs SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows.
General characteristics in patients with psoriasis and control subjects
Epidemiological data of patients with psoriasis and control subjects
Patients with psoriasis (n = 35)
Control subjects (n = 35)
Age (years) (mean ± SD)
43.94 ± 8.7
40.70 ± 13.686
Sex (male/female) %
21/14 (60/40) %
20/15 (57.1/42.9) %
Duration of disease (years) (mean ± SD)
9.80 ± 10.879
PASI score (mean ± SD)
9.78 ± 7.3
BMI value (mean ± SD)
29.01 ± 5.882
28.09 ± 2.9
WC (cm) (mean ± SD)
96.49 ± 18.442
93.12 ± 11.604
Hypertension (yes/no) %
9/26 (25.7/74.3) %
7/28 (20/80) %
Dyslipidaemia (yes/no) %
17/18 (48.6/51.4) %
15/20 (42.9/57.1) %
Diabetes mellitus (yes/no) %
13/22 (37.1/62.9) %
6/29 (17.1/82.9) %
Insulin resistance (HOMA-IR) (yes/no) %
15/20 (42.9/57.1) %
6/29 (17.1/82.9) %
History of ischemic heart disease (yes/no) %
4/31 (11.4/88.6) %
3/32 (8.6/91.4) %
Metabolic syndrome (yes/no) %
11/24 (31.4/68.6) %
5/30 (14.3/85.7) %
Smoking (yes/no) %
14/21 (40/60) %
15/20 (42.9/57.1) %
The mean PASI in patients was 9.78 ± 7.3, where 25 patients (71.43 %) had mild disease and 10 patients (28.57 %) had moderate to severe disease. The presence of IR in psoriasis patients was associated with significantly higher values of PASI (p = 0.046). Psoriasis patients with MetS had significantly higher values of PASI when compared to patients without MetS (13.6 ± 8.8 and 6.85 ± 3.9, respectively) (p = 0.032).
Levels of OPN in plasma
Higher levels of plasma OPN were significantly more detected in psoriasis patients with MetS when compared to patients without MetS (104.3 ± 23.05 and 84.12 ± 17.3 ng/mL, respectively) (p = 0.007).
In controls, plasma OPN correlated positively only with MetS (r = 0.364, p = 0.046).
Analyses of multivariate stepwise regression of factors affecting the level of plasma OPN showed that elevated plasma OPN was significantly associated with the occurrence of psoriasis (OR 0.494, 95 % CI 24.873–40.412, p < 0.001), high PASI (OR 0.465, 95 % CI 1.741–3.028, p < 0.001) and the presence of MetS (OR 0.155, 95 % CI 4.895–18.934, p = 0.001).
Levels of adiponectin in plasma
We detected significantly lower levels of plasma adiponectin in psoriasis patients with MetS when compared to patients without MetS (3.95 ± 1.1 and 4.87 ± 1.1 ng/mL, respectively) (p = 0.03).
In controls, plasma adiponectin negatively correlated with BMI (r = −0.552, p = 0.001), and MetS (r = −0.360, p = 0.034).
Analyses of multivariate stepwise regression for factors affecting the plasma levels of adiponectin showed that low plasma adiponectin was significantly associated with high PASI (OR −0.643, 95 % CI −180.646: −104.595, p < 0.001) and the presence of MetS (OR −0.257, 95 % CI −1.289: −257.405, p = 0.004).
In the current work, psoriatic patients showed significantly elevated levels of OPN and significantly depressed levels of adiponectin which were significantly associated with a higher PASI and the occurrence of MetS in comparison to the controls, further incriminating them in the complexity of psoriasis in agreement with other studies [5, 6, 7, 10, 17, 26, 29, 30, 31]. Furthermore, the presence of a negative correlation between plasma OPN and adiponectin being detected only in psoriatic patients in the current study is of particular interest as it refers to a possible interplay between both culprits in the context of psoriasis.
We postulate that the psoriatic micro environment might be responsible for this interplay especially that the included psoriatic patients and controls were selected to be of comparable BMI aiming to rule out the influence of the adipose tissue on the levels of both OPN  and adiponectin [32, 33]. The inflammatory milieu present in psoriasis might be one of the responsible factors, where the environment is rich in inflammatory cells, such as macrophages, natural killer cells and T lymphocytes , which are known to be among the cells responsible for the expression of OPN . Moreover, the up-regulation of inflammatory cytokines detected in psoriasis, such as interleukin-6 (IL)-6, is known to inversely correlate with the adiponectin level [29, 31]. Another possible attributing factor is hypothesized to be the renin–angiotensin–aldosterone system (RAAS), which has been shown to be enhanced in psoriatics  and might in turn induce OPN expression [23, 25] on one hand, and has a direct effect on reducing adiponectin expression on the other hand . Still a limitation in the current study is that the expression of the RAAS was not investigated.
This interaction between OPN and adiponectin seems to be reflected on the psoriatic events as both culprits appear to be entangled in the same pathogenetic pathways in psoriasis but in opposing directions. First, OPN is a keratinocyte proliferative inducer, and a recent study demonstrated its relation to Ki-67 (proliferation index) , whereas adiponectin possesses suppressive effects on hyperkeratosis and studies revealed that adiponectin enhances apoptosis of keratinocytes . The unchecked proliferation of keratinocytes in psoriasis  could be a reflection to this misbalance between both opponents. Second, OPN is a proangiogenic factor  and one study demonstrated that OPN expression seems to be related to the CD34 expression (angiogenesis marker) , whereas adiponectin exerts anti-angiogenic effects through apoptosis of endothelial cells . Again the misbalance between both culprits could be one of the causes responsible for the neo-angiogenesis which is regarded as a cornerstone in the psoriatic story . Third, OPN is a proinflammatory agent and participates in the upregulation of T helper (Th) cell lineages, among which are the Th1 and Th17 cells , while adiponectin has been shown to exert anti-inflammatory effects . Therefore, this misbalance could be partially translated into the inflammatory milieu evident in psoriasis . This creates an interesting closed circuit where the inflammatory milieu in psoriasis could be both the result and the cause for this interplay between OPN and adiponectin. Furthermore, in the current study, PASI positively correlated with plasma OPN level on one hand and negatively correlated with plasma adiponectin on the other hand, thus reflecting their impact on the severity of the disease. Moreover, it could be hypothesized that adiponectin might play a role in the chronicity of the disease through the detected negative correlation between adiponectin and disease duration.
The significant association detected in the current study between the occurrence of MetS and/or its components on one hand and the elevation of OPN or the reduction of adiponectin on the other hand further suggests that this correlation is not only restricted to the psoriatic process, but might also be related to the MetS commonly associated with it. The possible role of OPN and adiponectin in MetS is supported by several previous reports [6, 7, 19, 30]. Moreover, it has been shown that OPN decreases insulin resistance , meanwhile adiponectin was demonstrated to be able to improve it . Again those antagonizing actions of both OPN and adiponectin shed light on the inverse relations between both of them.
In conclusion, the current study demonstrates for the first time a significant negative correlation between OPN and adiponectin in psoriasis, highlighting a possible interplay that could be reflected on the pathogenesis of psoriasis and MetS and/or its components, adding more to the complexity of this multifactorial disease.
Conflict of interest
The authors declare that they have no conflict of interest.
- 10.El-Eishi NH, Kadry D, Hegazy RA, Rashed L (2012) Estimation of tissue osteopontin levels before and after different traditional therapeutic modalities in psoriatic patients. J Eur Acad Dermatol Venereol. doi:10.1111/j.1468-3083.2011.04417.x
- 33.Tilg H, MOschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6: 772–783Google Scholar