Polycystic ovary syndrome is associated with increased osteopontin levels

Saklamaz, Ali; Çalan, Mehmet; Yılmaz, Özgür; Küme, Tuncay; Temür, Muzaffer; Yıldız, Nurdan; Kasap, Esin; Genç, Mine; Yürekli, Banu Şarer; Kocabaş, Gökçen Ünal

doi:10.1530/eje-15-1074

Cited by 11 publications

(16 citation statements)

References 32 publications

(45 reference statements)

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“…In the present study, there was no significant difference in serum OPN levels between non-obese PCOS and control women. This finding is inconsistent with that of a recent study showing that PCOS is associated with increased serum OPN levels [ 33 ]. The major discrepancy may be due to the relatively low BMI and comparable HOMA-IR in our cohort.…”

Section: Discussioncontrasting

confidence: 99%

“…We found that an increased circulating OPN level was more common in higher FAI groups and associated with high degree of FAI in non-obese PCOS patients. This finding is consistent with a recent study that showed that OPN levels are associated with free testosterone levels [ 33 ]. In the BMI subgroup analysis, OPN levels were significantly higher in the overweight PCOS group compared to the lean PCOS group, while this difference was not found in control women.…”

Section: Discussionsupporting

confidence: 94%

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Circulating osteopontin and its association with liver fat content in non-obese women with polycystic ovary syndrome: a case control study

Wang

Zhou

et al. 2018

Reprod Biol Endocrinol

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BackgroundOsteopontin (OPN) plays an important role in inflammatory processes and insulin resistance. Polycystic ovary syndrome (PCOS) is a reproductive metabolic disease associated with insulin resistance and metabolic abnormalities, including high levels of liver fat content (LFC). The objective of this study was to explore whether circulating OPN independently contributes to elevated LFC in non-obese PCOS patients.MethodsThis study included 61 non-obese PCOS patients and 56 age-matched healthy women from Shanghai, China. After an overnight fast, all participants underwent anthropometric measurements, oral glucose tolerance tests, lipid profile and sex hormone measurements. Quantitative measurement of LFC by ultrasonography was performed. OPN concentrations were measured using ELISA. An independent samples t-test and the Mann-Whitney U test were performed to compare variables between the two groups; one-way ANOVA and Kruskal-Wallis test were performed to compare four subgroups of patients. Correlations were determined by Spearman’s correlation tests. Stepwise multiple linear regression analyses were performed to assess for independent contributors. A receiver operating characteristic curve with the maximum Youden index was calculated for the optimal cut-off value.ResultsIn non-obese PCOS women, circulating OPN levels were increased in the subgroups with a higher body mass index (BMI) and free androgen index (FAI), and the LFC levels were increased in the elevated OPN subgroups. Moreover, increased OPN was associated with increased FAI and LFC in PCOS women, and the association between OPN and LFC was independent of triglyceride, HOMA-IR and FAI after adjusting for PCOS status in all participants. OPN combined with FAI and hsCRP may better predict NAFLD than WHR in this study cohort. However, there was no significant difference in circulating OPN levels between non-obese PCOS and normal control women.ConclusionsIncreased OPN levels may be related to FAI and elevated LFC in non-obese women with PCOS.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0331-4) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 94%

Circulating osteopontin and its association with liver fat content in non-obese women with polycystic ovary syndrome: a case control study

Wang

Zhou

et al. 2018

Reprod Biol Endocrinol

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“…These results suggest that the presence of OPN at the endometrial surface is dependent on the expression of its receptor CD44 at the endometrial epithelial cell membrane. Interestingly, these findings agree with studies that reveal that interaction between CD44 and OPN represents a crucial ligand-receptor pair that facilitates systemic insulin resistance [36,37].…”

Section: Discussionsupporting

confidence: 90%

Differential regulation of osteopontin and CD44 correlates with infertility status in PCOS patients

et al. 2020

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Endometrial receptivity is mediated by adhesion molecules at the endometrium-trophoblast interface where osteopontin (OPN) and CD44 form a protein complex that plays an important role in embryo recognition. Here, we undertook a prospective study investigating the expression and regulation of OPN and CD44 in 50 fertile and 31 infertile ovulatory polycystic ovarian syndrome (PCOS) patients in the proliferative and secretory phases of the natural menstrual cycle and in 12 infertile anovulatory PCOS patients. Endometrial biopsies and blood samples were evaluated for expression of OPN and CD44 using RT-PCR, immunohistochemistry and ELISA analysis to determine circulating levels of OPN, CD44, TNF-α, IFN-γ and OPN and CD44 levels in biopsy media. Our findings highlighted an increased level of circulating OPN and CD44 in serum from infertile patients that inversely correlated with expression levels in endometrial tissue and positively correlated with levels secreted into biopsy media. OPN and CD44 levels positively correlated to each other in serum and media from fertile and PCOS patients, as well as to circulating TNF-α and IFN-γ. In vitro analysis revealed that hormone treatment induced recruitment of ERα to the OPN and CD44 promoters with a concomitant increase in the expression of these genes. In infertile patients, inflammatory cytokines led to recruitment of NF-κB and STAT1 proteins to the OPN and CD44 promoters, resulting in their overexpression. These observations suggest that the endometrial epithelial OPN-CD44 adhesion complex is deficient in ovulatory PCOS patients and displays an altered stoichiometry in anovulatory patients, which in both cases may perturb apposition. This, together with elevated circulating and local secreted levels of these proteins, may hinder endometrium-trophoblast interactions by saturating OPN and CD44 receptors on the surface of the blastocyst, thereby contributing to the infertility associated with ovulating PCOS patients. Key messages • Endometrial epithelial OPN-CD44 adhesion complex levels are deficient in ovulatory PCOS patients contributing to the endometrial infertility associated with ovulating PCOS patients. • Circulating levels of OPN, CD44 and inflammatory cytokines TNF-α and IFN-γ are altered in infertile PCOS patients. • Increased levels of both OPN and CD44 in biopsy media and serum inversely correlate with endometrial expression of these markers in endometrial tissue. • In infertile PCOS patients, high levels of oestrogens and inflammatory cytokines stimulate the recruitment of transcription factors to the OPN and CD44 promoters to enhance gene transcription. • Our study identifies a novel crosstalk between the CD44-OPN adhesion complex, ERα, STAT1 and NF-κB pathways modulating endometrial receptivity.

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“…Despite speculative, it is likely that in healthy young women OPN does not reflect an increased CV risk (atherosclerosis is expected to be very initial), but rather a response to hormonal or environmental factors. [23][24][25][26] Conversely, the strong positive association between OPN and CCA-IMT observed in patients further indicates SLE as a surrogate of a more advanced CV disease independently of age. 27 In this context, OPN would act as an active proatherosclerotic factor, as previously suggested.…”

Section: Discussionmentioning

confidence: 98%

“…Furthermore, the characteristics of the study cohort we investigated young women (with SLE or healthy controls) might potentially explain the opposite association between OPN and CCA‐IMT observed in the two study groups. Despite speculative, it is likely that in healthy young women OPN does not reflect an increased CV risk (atherosclerosis is expected to be very initial), but rather a response to hormonal or environmental factors . Conversely, the strong positive association between OPN and CCA‐IMT observed in patients further indicates SLE as a surrogate of a more advanced CV disease independently of age .…”

Section: Discussionmentioning

confidence: 99%

Serum osteopontin negatively impacts on intima‐media thickness in patients with systemic lupus erythematosus

Carbone

Dallegri

Montecucco

et al. 2019

Eur J Clin Investigation

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Background Ultrasound evaluation of carotid intima‐media thickness (cIMT) has been extensively used for potentially improving cardiovascular (CV) risk stratification in several patients’ categories. Subjects with systemic lupus erythematosus (SLE) have been investigated by both imaging and molecular biomarker approaches with contrasting results. Here, we focused on the role of osteopontin (OPN) as biomarker of subclinical atherosclerosis associated with SLE. Materials and Methods Eighty females (age 18‐65 years) affected by SLE and eighty age‐matched healthy female controls without a clinical history of CV disease underwent ultrasound evaluation of cIMT and blood sample assay of high‐sensitivity C‐reactive protein (hs‐CRP) and OPN. Results Healthy controls and SLE patients significantly differed for CV risk factors (ie, waist circumference, hypertension and dyslipidaemia) and the inflammatory status. Noteworthy, an opposite association between cIMT and OPN was observed in the two study groups. Whereas OPN was positively associated with mean cIMT (r = 0.364; P = 0.001) in SLE patients, a negative correlation was found in healthy controls. Furthermore, in SLE patients increased circulating levels of OPN were associated with the use of hydroxychloroquine and the positivity for the anti‐dsDNA autoantibodies. At linear regression analysis, only OPN remained independently associated with cIMT also after adjustment for age, smoking pack‐year, Heart SCORE, disease length and steroid therapy length. Conclusions These results indicate that serum OPN levels were strongly associated with subclinical atherosclerosis in patients with LES and it might be a useful CV biomarker that requires additional validation in larger trials.

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Polycystic ovary syndrome is associated with increased osteopontin levels

Cited by 11 publications

References 32 publications

Circulating osteopontin and its association with liver fat content in non-obese women with polycystic ovary syndrome: a case control study

Circulating osteopontin and its association with liver fat content in non-obese women with polycystic ovary syndrome: a case control study

Differential regulation of osteopontin and CD44 correlates with infertility status in PCOS patients

Serum osteopontin negatively impacts on intima‐media thickness in patients with systemic lupus erythematosus

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