Yazar "Doğan, Mustafa" seçeneğine göre listele

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    45,X[75]/46,Xdel(X)(p11.2)[25] Karyotipine sahip unikornuat uteruslu olgu
    (2019) Eröz, Recep; Köksal, Mehmet; Doğan, Mustafa; Yüce, Hüseyin; Başbuğ, Alper
    Turner sendromu, önemli bir infertilite nedenidir ancak mozaik veya X delesyonu taşıyan hastalarda eğer puberteye spontan olarakgirilmişse gebelik gerçekleşebilmektedir. Unikornuat uterus ise gebelik kaybına yol açabilen ve çok nadir rastlanılan bir uterusanomalisidir. Şu anki olgu, nadir görülmesi ve Turner sendromlu hastalarda gebelik kayıplarının bir nedenin ortaya konması gibiyönleriyle literatüre katkı sağlamak amacıyla sunulmuştur.
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    Atypical presentation in patients with 17 ?-hydroxylase deficiency caused by a deletion in the CYP17A1 gene: short stature
    (2020) Bolu, Semih; Eröz, Recep; Tekin, Mehmet; Doğan, Mustafa
    Background. Patients with 17?-hydroxylase deficiency (17 OHD) usually present with tall stature and eunuchoid features, rather than growth retardation. However, unlike the classic form of the disease, short stature due to a lack of pubertal growth spurt and sex hormone deficiency was present in our four cases. We wanted to emphasize that short stature might be the cause of first presentation in patients with 17 OHD. Cases. We report five patients of Kurdish origin with 17 OHD, four of whom had short stature; two presented because of short stature and two were detected as having short stature. The external genitalia had a female appearance and was prepubertal in all cases. Hypertension was also detected in four of the patients. Serum biochemical and hormonal analyses were performed for each patient. Laboratory data suggesting severe growth hormone (GH) deficiency were obtained from one patient, while the other had a familial history suggesting constitutional delay of growth and puberty (CDGP). Whole exome sequence analysis of the CYP17A1 gene was performed on all patients. STR fragment analysis and multiplex ligation dependent probe amplification (MLPA) analysis was also performed to detect mutations associated with congenital adrenal hyperplasia (CAH) in the CYP17A1 gene. No mutation was detected in the whole exome sequence analysis of the CYP17A1 gene in all five patients, although wide deletions were identified in the 1st–6th exons of this gene at MLPA analysis. Conclusions. Patients with 17?-hydroxylase deficiency can present with short stature because they have no pubertal growth spurt during adolescence. Therefore, 17 OHD should be considered in the differential diagnosis of patients with delayed puberty and short stature.
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    Bilateral Sprengel Deformite, Konjenital Tek Taraflı Böbrek Agenezisi, MEFV Geninde M680İ (GC)Heterozigot Mutasyonu Olan Klippel-Feil Sendromlu Yedi Yaşında Bir Kız Olgu
    (2017) Doğan, Mustafa; Bolu, Semih; Yüce, Hüseyin; Eröz, Recep
    KFS, kısa boyun, düşük arka saç çizgisi ve boyun hareketlerini kısıtlayan servikal vertebraların füzyonuyla karakterizedir. Biz bilateral Sprengel deformiteli, konjenital tek taraflı böbrek agenezisi ve MEFV gen mutasyonu olan bir bayan KFS'li vakayı sunduk. Hastanın fizik muayenesi, rutin biyokimyasal, radyolojik değerlendirilmesi yapıldı ve aile öyküsü alındı. İlaveten, kromozomal analiz, MEFV geninin tüm ekzom sekans analizi ve GDF6 geninin sekans analizi yapıldı. Hastada kısa boyun, baş ve boyun hareketleri kısıtlanmış, düşük posterior saç çizgisi, bilateral Sprengel deformitesi, hafif skolyoz ve konjenital tek taraflı renal agenezisi vardı. Ayrıca hastanın parsiyel vertebra füzyonu vardı. Hasta, servikal kifoz, spinal kanalın füziform genişlemesi, servikal spinal kordun artmış kalınlığı, spinal kordun merkezinde yaklaşık 1.5 cm'ye ulaşan kistik genişlemeye ve normal karyotipe sahipti. Vakanın M680I(GC) mutasyonu vardı. Vakanın GDF6 geni analiz sonucu normaldi. Bildiğimiz kadarıyla bu; KFS, bilateral Sprengel deformite, konjenital tek taraflı renal agenezi ve FMF mutasyonunun birlikte olduğu ilk vakadır. KFS'li olgularda nörolojik defisitlerin minör travma sonrası görülmesi nedeniyle hasta, dikkatli olmalı ve ağır egzersizden kaçınmalıdır. Hastanın karaciğerinde ve dalağında kistler ve aile geçmişinde böbrek yetmezliği vardı. Bu nedenle hasta polikistik böbrek rahatsızlığı açısındanda değerlendirilmektedir. Bunlara ilaveten, vaka MEFV geninde mutasyona sahip olduğundan, amiloidozis riski için hasta yaşamı süresince böbrek rahatsızlığı açısından takip edilmelidir.
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    A boy with short stature, unusual findings and low percentage of 45,X(4%) / 46,XY(96%) mosaicism
    (Editions Medecine et Hygiene, 2016) Doğan, Mustafa; Eröz, Recep; Bolu, Semih; Yüce, Hüseyin; Gün, Emrah
    [No abstract available]
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    A BOY WITH SHORT STATURE, UNUSUAL FINDINGS AND LOW PERCENTAGE OF 45,X(4%)/46,XY(96%) MOSAICISM
    (Medecine Et Hygiene, 2016) Doğan, Mustafa; Eröz, Recep; Bolu, Semih; Yüce, Hüseyin; Gün, Emrah
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    A case with pseudohypoaldosteronism type 1 and investigation of molecular genetic etiology
    (Duzce University Medical School, 2017) Bolu, Semih; Doğan, Mustafa; Eröz, Recep; Yüce, Hüseyin; Mermerci, Asuman; Özmerdivenli, Recep
    Pseudohypoaldosteronism is a salt-wasting pattern that manifests with hyponatremia, hyperkalemia, and metabolic acidosis, and is the result of aldosterone peripheral nonresponse in renal tubule cells. Peripheral resistance development may occur as a result of mutations in the mineralocorticoid receptor or epithelial sodium channel; it can also develop as a secondary to infection, uropathy and receptor resistance due to drug use. Type 1 PHA is inherited as both autosomal dominant (sporadic-renal form) and autosomal recessive (systemic form). Systemic pseudohypoaldosteronism type 1 is autosomal recessive and the most severe form. Loss of function in one of the three subunits of the epithelial sodium channel (EnaC) is responsible for the disease (the alpha subunit (SCNN1A; 12p13), the beta subunit (SCNN1B; 16p12.2-p12.1), and the Gamma subunit (SCNN1G; 16p12). We present a patient who was diagnosed the primary pseudohypoaldosteronism type 1 for contribution to the literature, which is a rare disease and can be confused with other diseases caused by salt loss. © 2017, Duzce University Medical School. All rights reserved.
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    Clinical findings and BTD gene molecular analysis results of patients presenting with suspicion of biotinidase deficiency
    (Duzce University Medical School, 2018) Eröz, Recep; Turan, Betül; Doğan, Mustafa; Yüce, Hüseyin; Kocabay, Kenan; Özmerdivenli, Recep
    Aim: Biotinidase deficiency is an autosomal recessive disease, also known as late-onset biotin-sensitive multiple carboxylase deficiency caused by pathogenic mutations in the biotinidase (BTD) gene responsible for the production of biotinidase. In this study, we aimed to present the clinical findings and BTD gene molecular analysis results in the light of the literature. Material and Methods: Nine patients who were positive in heel blood screening and cases compatible with neurological, sensory, metabolic, respiration and skin findings of biotinidase deficiency were included in the study. For the isolation of genomic DNA from the participants included in the study, 2 cc of peripheral blood was taken into Ethylene Diamine Tetra Acetic Acid (EDTA) tubes and their genomic DNA was isolated and sequence analysis of the BTD gene was performed. Results: According to the all exon sequence analysis results of the BTD gene, homozygous c.1368A>C/p.Gln456His mutation was detected in 1 patient; heterozygous c.1368A>C/p.Gln456His mutation was detected in 1 patient; combined heterozygous c.1330G>C/p.Asp444His and c.511G>A/p.Ala171Thr mutations were detected in 1 patient, combined heterozygous c.1336G>C/p.Asp446His and c.511G>A/p.Ala171Thr were detected in 1 patient, and c.557G>A/p.Cys186Tyr mutation was detected in 1 patient. No mutation was detected in 4 patients. Conclusion: Early diagnosis and treatment are very important for eliminating the problems experienced by patients with BTD disorder and for preventing complications that may occur in case of delay. It is important that informing the patient and family members about the prenatal diagnosis or preimplantation genetic diagnosis method for autosomal recessive inherited disease by giving genetic counseling. © 2018, Duzce University Medical School. All rights reserved.
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    Dirençli epilepside akılda tutulması gereken tanı; tuberoskleroz
    (2022) Kurt, Fatih; Eröz, Recep; Doğan, Mustafa
    İlaca Dirençli epilepsi; nöbet tipine uygun seçilmiş, tolere edilebilen iki antiepileptik ilacın uygun doz ve sürede verilmesine rağmen nöbetlerin devam etmesidir. Gelişme geriliği, fokal nörolojik bulguların olması, organik beyin lezyonu olması, spesifik EEG bozukluğu ve ailede epilepsi varlığı dirençli epilepsi açısından risk faktörleridir. Tüberoskleroz hastalığı deri, merkezi sinir sistemi, böbrek ve akciğer gibi birçok organda hamartomlarla seyreden, multisistemik, otozomal dominant geçişli genetik bir hastalıktır. Tuberoskleroz hastalığında görülen beyin hamartomları ve diğer santral sinir sistemi lezyonları dirençli epilepsinin ortaya çıkmasına neden olmaktadır. Bu yazıda dirençli epilepsi tanısıyla takip edilen, tipik fizik muayene bulguları olmasına rağmen 16 yaşında Tuberoskleroz tanısı alan hasta sunuldu. Dirençli epilepsi etyolojisinde Tuberosklerozun akılda tutulması gerektiği ve fizik muayenenin ne kadar önemli olduğunu tekrar vurgulanmak istendi.
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    Effect of adiponectin on a disintegrin and metalloproteinase with thrombospondin motifs-9 gene expression in human chondrocytes
    (Amer Assoc Immunologists, 2014) Yaykaşlı, Kürşat Oğuz; Doğan, Mustafa; Hatipoğlu, Ömer; Yaykaşlı, Emine; Kaya, Ertuğrul; Özşahin, Mustafa; Uslu, Mustafa
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    Evaluation of Karyotype Composition of Our Turner Syndrome Patients with Their Application Complaints and Anthropometric
    (Duzce Univ, 2018) Doğan, Mustafa; Eröz, Recep; Bolu, Semih; Yüce, Hüseyin
    Objective: Turner syndrome (TS) is the result of partial or complete loss of the second X chromosome in women or structural anomalies of the X chromosome, and is characterized by clinical manifestations such as short stature, lymphedema, cardiac anomalies, primer over failure and neurocognitive problems. We have presented our patients with Turner syndrome together with the reasons for application complaints and anthropometric datas with karyotype compositions for contribution to the literature. Method: DNA was isolated from the peripheral blood samples and chromosome analysis were performed in the patients who were thoought to be Turner Syndrome at Duzce University Medical Faculty Medical Genetics Department. Twenty patients who were compatible with Turner's syndrome were included in the study. The complaints, height, weight, BMI (body mass index) values of each case included in the study were noted. Results: According to the results of cytogenetic analysis in our study, it was detected that 9 patients were 45, X (45%), 1 patient was 46, X, der(X), t(X,X)(p.11.2;q22)/45,X (%5), 1 patient was 45, X/46, X,del(X)(p.11.2) (%5), 1 patient was 45, X/47,XXX (%5), 4 patients were 45, X/46,XX (%20), 2 patients were 46,X,i(X)(q10)/45,X (%10), 1 patient was 46,X,i(X)(q10) (%5), 1 patient was 46, X, del(X)(p21) (% 5) chromosomal composition. Conclusion: Patients with TS show different karyotype compositions, which cause different clinical manifestations in patients. The "45, X" karyotype was found to be significantly higher than other chromosomal compositions, and the most common complaint in our patient group was short stature of 60%. Karyotype analysis is important for early diagnosis and early treatment in patients being followed up with short stature etiology. Patients should be followed up with a multidisciplinary team approach on a regular basis
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    A FAMILY FROM TURKEY WITH 761_764DUPCCGC (p.ASN256ARGFS70,c.761_764DUPCCGC) MEFV GENE MUTATION, THEIR CLINICAL FEATURES AND REVIEW OF THE LITERATURE
    (Duzce Univ, 2016) Eröz, Recep; Doğan, Mustafa; Yüce, Hüseyin; Özmerdivenli, Recep
    Familial Mediterranean Fever (FMF) is an autosomal recessive hereditary disease that mainly affects Armenian, Jewish, Turkish and Arab populations and the most common and best understood periodic fever disease. The Mediterranean Fever (MEFV) gene is responsible for the disease. This gene including 10 exon and placed on chromosome 16p13.3. A family from Turkey with a total of five members clinically diagnosed as FMF are examined. All exom sequencing analysis of MEFV gene was done for all family members. According to our results, a 761_764dupCCGC (p.Asn256Argfs70,c.761_764dupCCGC) duplication mutation was detected in exon 2 of MEFV gene. Although our proband, his brother, sister and father have carried this mutation, the probands' mother has not any mutation. There is only one case with this mutation (HGMD no: CI055758) in the literature and limited information about clinical datas of the patient was shared. The proband has no family history of FMF but has chest and abdominal pain. Interestingly, the others family members with this mutation has no clinical findings for FMF. According to the PolyPhen-2 and Mutation Taster bioinformatics programs, this duplication seems to be pathogenic. Futher studies are needed to obtain more clear information about the 761_764dupCCGC mutation. We thought that this duplication mutation may give significant knowledge for future research on FMF pathogenesis.
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    A family with novel homozygous deletion mutation (c.1255delT; p.Phe419Serfs*12) in the glucokinase gene, which is a rare cause of permanent neonatal diabetes mellitus
    (2020) Bolu, Semih; Eröz, Recep; Doğan, Mustafa; Arslanoğlu, İlknur; Uzun, Hakan; Timur, Furkan
    Heterozygous inactivating mutations in the glucokinase gene cause the mildest form of maturity-onset diabetes of the adolescents. However, homozygous or compound heterozygous mutations in the glucokinase gene are a rare cause of permanent neonatal diabetes mellitus. Herein, we present the case of a male child with permanent neonatal diabetes mellitus whose mutational analysis revealed a novel homozygous deletion mutation in the glucokinase gene. The male proband of Turkish ancestry from consanguineous parents was born at 37 weeks gestation with a birth weight of 1870 g (<3rd percentile). Hyperglycemia developed during the first postnatal day and diabetes-related autoantibodies were negative. He was put on insulin on the first day of life. Insulin has never been discontinued since then. The mother was aged 35 years and had gestational diabetes. The father and the two brothers had impaired fasting glucose. Both parents and brothers were heterozygous for this mutation.
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    A family with novel homozygous deletion mutation(c.1255delT; p.Phe419Serfs*12) in the glucokinasegene, which is a rare cause of permanent neonataldiabetes mellitus
    (2020) Doğan, Mustafa; Uzun, Hakan; Arslanoğlu, İlknur; Timur, Furkan; Bolu, Semih; Eröz, Recep
    Heterozygous inactivating mutations in the glucokinase gene cause the mildest form of maturity-onset diabetes of the adolescents. However, homozygous or compound heterozygous mutations in the glucokinase gene are a rare cause of permanent neonatal diabetes mellitus. Herein, we present the case of a male child with permanent neonatal diabetes mellitus whose mutational analysis revealed a novel homozygous deletion mutation in the glucokinase gene. The male proband of Turkish ancestry from consanguineous parents was born at 37 weeks gestation with a birth weight of 1870 g (<3rd percentile). Hyperglycemia developed during the first postnatal day and diabetes-related autoantibodies were negative. He was put on insulin on the first day of life. Insulin has never been discontinued since then. The mother was aged 35 years and had gestational diabetes. The father and the two brothers had impaired fasting glucose. Both parents and brothers were heterozygous for this mutation.
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    Klinik olarak mody diyabeti olduğu düşünülen türk çocuklarında hedefe yönelik yeni nesil dizi analizi yöntemiyle moleküler tanının ortaya konması
    (Düzce Üniversitesi, 2017) Doğan, Mustafa; Yüce, Hüseyin
    Diyabet özellikle çocukluk çağında klinik ve etyopatogenetik heterojenite gösteren ağır bir kronik hastalıktır. Maturity Onset Diabetes of the Young (MODY) otozomal dominant kalıtım paternine sahip ve belirgin genetik heterojenitesi olan bir diyabet tipidir. MODY'nin moleküler genetik tanısı optimal tedavi, prognoz ve genetik danışmanlık için gereklidir. Etyolojisi genetik heterojenite gösteren hastalıklar için NGS yöntemi(yeni jenerasyon dizi analizi) uygulanması en ideal yöntem olarak karşımıza çıkmaktadır. Biz bu çalışmamızda klinik olarak MODY diyabet şüphesiyle takipli olan hastalarımızda, NGS ile genetik etyolojiyi ortaya çıkarmak ve genotip–fenotipilişkisini değerlendirmeyi amaçladık. Klinik olarak MODY diyabet şüphesi olan 35 hasta çalışmaya dahil edilmiştir. Aday hastalar 400 olgunun kayıtlı olduğu Düzce Üniversitesi Tıp Fakültesi Çocuk Endokrin Bilim Dalı çocuk diyabeti veri tabanından aile öyküsü, vücut ağırlığı, ketoza yatkınlık, insülin, C-peptid ve otoantikor varlığı özelliklerine göre en uygun olanlardan seçilmiştir. Hastalardan periferik kan örneği alınarak DNA izole edilmiş ve MODY etyolojisinde ortaya konmuş olan 13 adet GCK, HNF1A, HNF4A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8 ve KCNJ11 genleri NGS yöntemiyle çalışılmış, saptanan varyantlar yine NGS ile doğrulanmıştır. Saptanan varyantların biyoinformatik ve in-siliko analiz verileri, segregasyon çalışmaları ve hastaların klinik ve laboratuvar bulguları birlikte değerlendirilerek patojenitesine karar verildi. 11 hastada(%31) bakılan MODY genlerinde mutasyon saptanmıştır.2 hastada GCK, 2 hastada CEL,1'er hastada ise HNF1A,KLF11,BLK,NEUROD1, ABCC8, 1 hastada ise HNF1A,HNF4A ve WFS1 geninde mutasyon tespit edildi. Hastaların 9'u heterozigotformda iken, 1 hasta birleşik heterozigot, 1 hasta ise kompleksgenotipe sahipti. Çalışmamızda GCK geni Ekzon 5'te c.537delG ve CEL geni Ekzon 6'da IVS5-1G>A olmak üzere daha önce tanımlanmamış iki yeni değişiklik tespit ettik. Klinik olarak MODY diyabeti, tip 1 ve tip 2 diyabetten ayırt etmek zor olduğundan, monojenik form diyabeti olan birçok hastanın yanlış sınıflandırılmakta olduğunu söyleyebiliriz. Her ne kadar MODY bütün diyabet vakalarının % 1-2'sini oluştursa da, MODY'nin moleküler genetik tanısı optimal tedavi, prognoz ve genetik danışmanlık için gereklidir. Türk toplumunda MODY diyabet ile ilgili daha fazla kişiyle yapılacak olan moleküler çalışmalarla ülkemize özgü değişiklikler ortaya konabilecek, yeni mutasyonlar tanımlanacak ve genotip-fenotip ilişkilendirmeleri daha doğru yapılabilecektir.
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    The known about next-generation sequencing (NGS) [Yeni nesil dizileme (YND) hakkında bilinenler]
    (Duzce University Medical School, 2017) Doğan, Mustafa; Eröz, Recep; Yüce, Hüseyin; Özmerdivenli, Recep
    The Next-Generation Sequencing (NGS) method is based on by forming a library with a plurality of DNA fragments by cutting the base DNA with enzymatic reactions and the amplification of DNA fragments constituting the library. According to OMIM statistics, there are now more than 6,000 single gene disorders and molecular basis of nearly two thirds of these disorder is unknown. A great deal of progress has begun to be made in understanding the molecular basis of many diseases depending on the development of NGS platforms. With NGS technology, in addition to whole genomes and whole exome sequencing, a large number of genes can be sequenced for the etiology of diseases with genetic heterogeneity using target-oriented NGS panels at the same time. With the description of genetic etiology that causes diseases, patients can be given more accurate genetic counseling and family members under risk can be quickly screened. It is possible to reveal the genetic basis of phenotypic and genotypic heterogeneous diseases with the development of new generation lineage analyzes. To the best of our knowledge, there are no Turkish review except for a few English review written about NGS so far. For this reason, it is tried to present to readers what is known about NGS in this review. © 2017, Duzce University Medical School. All rights reserved.
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    Leptin induction of aggrecanases-1 and-2 genes expression in human chondrocytes is mediated by p38 mitogen-activated protein kinase pathway
    (Amer Assoc Immunologists, 2014) Hatipoğlu, Ömer Faruk; Yaykaşlı, Kürşat Oğuz; Doğan, Mustafa; Yaykaşlı, Emine; Kaya, Ertuğrul; Özşahin, Mustafa; Usiu, Mustafa
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    MEFV Geni 761_764dupCCGC p.Asn256Argfs70, c.761_764dupCCGC Mutasyonlu Türkiyeden Bir Aile, Onların Klinik Özellikleri ve Literatür Taraması
    (2016) Eröz, Recep; Doğan, Mustafa; Yüce, Hüseyin; Özmerdivenli, Recep
    Ailesel Akdeniz Ateşi (FMF) primer olarak Musevi, Ermeni, Türk ve Arap populasyonunu etkileyen otozomal resesif geçişli bir otoenflamatuvar bir hastalıktır. FMF, Mediterranean Fever (MEFV) geni kromozom 16p13.3 bölgesinde yerleşen, 10 ekzondan oluşan hastalıktan sorumlu bir gendir. Klinik olarak FMF tanısı almış total 5 kişiden oluşan bir Türk ailesi incelendi. MEFV geninin tüm ekzom sekans analizi aile bireyleri için yapıldı. Bizim sonuçlarımıza göre, (p.Asn256Argfs70,c.761_764dupCCGC) duplikasyon mutasyonu tespit edildi. Proband, onun erkek kardeşi, kız kardeşi ve babası bu mutasyonu taşımasına rağmen, probandın annesi hiçbir mutasyon taşımıyordu. Literatürde bu mutasyonlu yalnızca bir hasta bildirilmiştir (HGMD no: CI055758) ve hastanın kliniğiyle ilgili sınırlı veri paylaşılmıştır. Probandın aile öyküsü yoktu fakat göğüs ve karın ağrısı vardı. İlginç olarak bu mutasyonlu diğer aile üyeleri FMF'in klinik bulgularına sahip değillerdi. PolyPhen-2 ve Mutation Taster bioinformatics programlarına göre bu duplikasyon patojenik olarak görünüyordu. 761_764dupCCGC mutasyonu hakkında daha açık bilgi elde edebilmek için ilave çalışmalara gereksinim vardır. Biz bu duplikasyon mutasyonunun FMF patogenezinde gelecekte yapılacak araştırmalar için önemli bilgiler sağlayacağını düşünüyoruz
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    NF-?B and MAPKs are involved in resistin-caused ADAMTS-5 induction in human chondrocytes
    (The Canadian Society for Clinical Investigation, 2015) Hatipoğlu, Ömer Faruk; Yaykaşlı, Kürşat Oğuz; Doğan, Mustafa; Yaykaşlı, Emine; Bender, Onur; Yaşar, Tuğçe; Gündüz, Mehmet
    Purpose: Chronic inflammation is an important etiological factor in the development of arthritic diseases. Several factors contribute to aggregation of chronic inflammation, including the presence of excess adipose tissue. Methods: The putative induction mechanisms of ADAMTS-5 by resistin were investigated in normal primary human articular chondrocytes. Expression levels of the ADAMTS-5 gene were determined at several resistin doses and durations. Results: Human chondrocytes were activated and associated with upregulated ADAMTS-5 gene expression after exposure to resistin (also known as adipose tissue-specific secretary factor, ADSF). Release of ADAMTS-5 leads to joint cartilage degradation, a key event in the development of arthritic diseases rheumatoid arthritis (RA) and osteoarthritis (OA). Activation of chondrocytes was associated with upregulated NF-?B protein levels in a time-dependent fashion. Co-incubation of human chondrocytes with JNK and p38 inhibitors lead to abrogated levels of NF-?B, indicating that these MAPKs are important in the activation of chondrocytes after stimulation with resistin. Similarly, ADAMTS-5 expression levels were abrogated when co-incubated with p38, NF-?B, JNK, MEK and PI3K inhibitors. Our results demonstrate that resistin, released from adipose tissue, may be involved in the development of RA and OA in obese patients through degradation of joint cartilage via ADAMTS-5 released from activated chondrocytes. © 2015 CIM.
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    NF-kappa B and MAPKs are involved in resistin-caused ADAMTS-5 induction in human chondrocytes
    (Canadian Soc Clinical Investigation, 2015) Hatipoğlu, Ömer Faruk; Yaykaşlı, Kürşat Oğuz; Doğan, Mustafa; Yaykaşlı, Emine; Bender, Onur; Yaşar, Tuğçe; Gündüz, Mehmet
    Purpose: Chronic inflammation is an important etiological factor in the development of arthritic diseases. Several factors contribute to aggregation of chronic inflammation, including the presence of excess adipose tissue. Methods: The putative induction mechanisms of ADAMTS-5 by resistin were investigated in normal primary human articular chondrocytes. Expression levels of the ADAMTS-5 gene were determined at several resistin doses and durations. Results: Human chondrocytes were activated and associated with upregulated ADAMTS-5 gene expression after exposure to resistin (also known as adipose tissue-specific secretary factor, ADSF). Release of ADAMTS-5 leads to joint cartilage degradation, a key event in the development of arthritic diseases rheumatoid arthritis (RA) and osteoarthritis (OA). Activation of chondrocytes was associated with upregulated NF-kappa B protein levels in a time-dependent fashion. Co-incubation of human chondrocytes with JNK and p38 inhibitors lead to abrogated levels of NF-kappa B, indicating that these MAPKs are important in the activation of chondrocytes after stimulation with resistin. Similarly, ADAMTS-5 expression levels were abrogated when co-incubated with p38, NF-kappa B, JNK, MEK and PI3K inhibitors. Our results demonstrate that resistin, released from adipose tissue, may be involved in the development of RA and OA in obese patients through degradation of joint cartilage via ADAMTS-5 released from activated chondrocytes.