The pathophysiology of the growth plate in juvenile idiopathic arthritis

MacRae, Vicky; Farquharson, Colin; Ahmed, S. Faisal

doi:10.1093/rheumatology/kei091

Cited by 60 publications

(53 citation statements)

References 132 publications

(137 reference statements)

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“…Chronic inflammatory diseases such as juvenile idiopathic arthritis and inflammatory bowel disease often lead to childhood growth retardation through a number of proposed mechanisms that includes nutritional deficiency, chronic inflammation, increased catabolism, defects in the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis and use of glucocorticoids (MacRae et al 2006a, Wong et al 2006. Levels of proinflammatory cytokines, such as tumour necrosis factor (TNF)-a and interleukin (IL)-1b are often raised in these diseases, and measures that block TNF-a action, such as anti-TNF therapy, lead to an improvement in growth.…”

Section: Introductionmentioning

confidence: 99%

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

MacRae¹,

Burdon²,

Ahmed³

et al. 2006

Journal of Endocrinology

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Proinflammatory cytokines inhibit growth plate development. However, their underlying mechanisms of action are unclear. These effects may be mediated by ceramide, a sphingosine-based lipid second messenger, which is elevated in a number of chronic inflammatory diseases. To test this hypothesis, we determined the effects of C2-ceramide, a cell permeable ceramide analogue, on the growth of the ATDC5 chondrogenic cell line and on cultured fetal mice metatarsals. In ATDC5 cells, C2-ceramide significantly induced apoptosis at both 40 (82%; P!0 . 05) and 25 mM (53%; P!0 . 05). At 40 mM, C2-ceramide significantly reduced proliferation ([ 3 H]-thymidine uptake/mg protein) (62%; P!0 . 05). C2-ceramide did not markedly alter the differentiation state of the cells as judged by the expression of markers of chondrogenesis and differentiation (sox 9, collagen II and collagen X). The IGF-I signalling pathway is the major autocrine/paracrine regulator of bone growth. Both in the presence and absence of IGF-I, C2-ceramide (25 mM) induced an equivalent reduction in proliferation (60%; P!0 . 001). Similarly, C2-ceramide (40 mM) induced a 31% reduction in fetal metatarsal growth both in the presence and absence of IGF-I (both P!0 . 001). Furthermore, C2-ceramide reduced ADCT5 proliferation in the presence of AG1024, an IGF-I and insulin receptor blocker. Therefore, C2-ceramide-dependent inhibition appears to be independent of IGF-mediated stimulation of bone growth. Indeed, biochemical studies demonstrated that C2-ceramide (25 mM) pretreatment did not alter IGF-I-stimulated phosphorylation of insulin receptor substrate-1, Akt or P44/42 MAP kinase. In conclusion, C2-ceramide inhibits proliferation and induces apoptosis in growth plate chondrocytes through an IGF-I independent mechanism.

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Section: Introductionmentioning

confidence: 99%

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

MacRae¹,

Burdon²,

Ahmed³

et al. 2006

Journal of Endocrinology

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“…İnflamasyonun RA'da yaygın olan subklinik vaskülite, endotel hasarına ve dislipideminin etkisiyle de hızlanmış ateroskleroza yol açtığı bilinmektedir (26). Kronik inflamatuvar hastalıklarda ortaya çıkan ve tüm vücudu etkileyen proinflamatuvar sitokinlerin artırdığı fibroblast aktivasyonu subendokardiyal bölgede fibrozise neden olmaktadır (27). Romatoid artrite bağlı ölümlerin yaklaşık %20'sinde miyokardiyal fibrozis, iskemiye bağlı miyosit yapısında bozulma ve inflamasyon bildirilmiştir (16,28).…”

Section: Discussionunclassified

Assessment of left ventricular functions with tissue Doppler, strain and strain rate echocardiography in children with juvenile idiopathic arthritis: An observational study

Yılmaz¹,

Ceylan²,

Örün³

et al. 2012

Anadolu Kardiyol Derg

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GirişJuvenil idiyopatik artirit sinoviyal dokuları tutan ve nedeni tam olarak bilinemeyen kronik, sistemik ve enflamatuvar bir hastalık olup, çocukluk çağı kronik artritlerinin en sık nedenidir (1, 2). Eklem bulguları daha fazla olmakla birlikte çoğu organ ve sistemi de tutabilen kronik bir hastalık şeklinde de ortaya çıkabi-lir (3, 4). Juvenil idiyopatik artritte kardiyak tutulum genellikle sessiz seyreder ancak yaşamı tehdit eden komplikasyonlar da görülebilir. Kardiyovasküler tutulumun değerlendirilmesinde ekokardiyografik inceleme bilinen bir yöntemdir (5). Önceki çalışmalarda JIA'lı çocuklarda sol ventrikül fonksiyonlarını değerlendirmek için klasik ekokardiyografik yöntemler kullanıl-mıştır (6). Klasik Doppler ekokardiyografi atriyoventriküler kapakların girimi ve pulmoner venöz akım velositelerinin ölçümüyle sol ventrikül fonksiyonlarını değerlendirmede oldukça yararlıdır (7-9). Ancak bu standart teknik sol atriyum basınçlarından, psö-donormalizasyon, miyokart relaksasyonundan ve volüm yüklen-melerinden etkilenmektedir (10, 11). Doku Doppler ekokardiyografi yerel miyokart segmentlerini değerlendirebilir ve miyokart fonksiyonlarını hesaplayabilir. Doku Doppler miyokart görüntüle-me tekniğinden türetilen 'strain' (gerilme) ve 'strain rate' (gerilme hızı) ölçümleri bölgesel deformasyonun yüzdesini ve deformasyon hızını ölçen yeni bir yöntem olarak geliştirilmiştir (12, 13). Şimdiye kadar JIA'lı çocuklarda bölgesel miyokart fonksiyonları-nı değerlendiren herhangi bir çalışma yapılmamıştır.Bu amaçla kardiyovasküler yönden asemptomatik ve standart ekokardiyografi bulguları normal olan JIA'lı hastalarda doku Doppler görüntüleme yöntemi ile bölgesel miyokart fonksiyonlarını ölçerek sol ventrikül segmentlerininin sistolik ve diyastolik fonksiyonlarını değerlendirmek istedik. YöntemlerÇalışma dizaynı Bu çalışma enine-kesitli gözlemsel olarak dizayn edildi. Çalışma için etik kurul onayı Ankara Üniversitesi Tıp Fakültesi'nden alındı. Ayrıca çalışmaya dahil edilen hastalardan bilgilendirilmiş onam formları alındı. Çalışma popülasyonu Bazal klinik özelliklerHastaların yaş, cinsiyet, ağırlık, boy, kalp hızı, ortalama kan basıncı, hastalık süresi, almakta olduğu kortikosteroidlerin ve hastalığı modifiye edici ilaçların (DMARDs: Disease-modifying antirheumatic drugs) kullanım süreleri sorgulandı. Hastaların hemoglobin (Hb), beyaz küre (BK), eritrosit sedimantasyon hızı (ESR), C-reaktif protein (CRP) düzeyleri değerlendirildi. Telekardiyografi ve elektrokardiyografileri çekildi. Tüm hastaların konvansiyonel ekokardiyografilerine ek olarak doku Doppler, gerilme ve gerilme hızı teknikleri uygulanarak sol ventrikül fonksiyonları değerlendirildi. EkokardiyografiJuvenil idiyopatik artritli hastalar ve kontrol grubundaki sağ-lam çocuklara nabız dalga doku Doppler ve gerilme/gerilme hızı ekokardiyografi ile ölçümler yapıldı. Çalışmaya dahil edilen hastalardan bir pediyatrik kardiyolog tarafından sırt üstü ve/veya sol yan yatar pozisyonda iken 3 MHz prob kullanılarak Vivid 7 (GE Medical Systems, Norway) ekokardiyografi cihazı ile ...

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“…Growth retardation may also be induced by prolonged use of corticosteroids, especially when initiated in the young age [8] [27]. Other pathophysiological mechanisms include other cytokineinduced epigenetic changes [34] and malnutrition [35].…”

Section: Pathophysiology Of Growth Retardation In Jiamentioning

confidence: 99%

Growth Pattern in Children with Juvenile Idiopathic Arthritis: A Retrospective Study

Alsulami¹,

Alsulami²,

Muzaffer³

2017

OJRA

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Aim of this study is to assess growth pattern in children with juvenile idiopathic arthritis (JIA) and factors associated with growth retardation. Methods: A retrospective chart review of all cases of JIA following up at Pediatric Department of King Abdulaziz University Hospital, between July 2000 to July 2016. Demographic, clinical and biological data were collected and analyzed as risk factor for growth retardation. These included age, gender, age at diagnosis, disease duration, type of JIA, the presence of uveitis, rheumatoid factor (RF) positivity, antinuclear antibody (ANA) titer and treatment. Growth pattern was assessed as the percentile for height-for-age, weight-for-age and weight-for-height in reference to the Growth Chart for Saudi Children and Adolescents. Change in percentile rank was divided into 3 categories: regression (a drop of ≥1 percentile); stable (uphold of the same percentile); and progression (change for a superior percentile). Results: A total 78 children were eligible, 52.6% females, mean ± SD age = 9.94 ± 4.92 years, and age at diagnosis = 7.44 ± 4.52 years, mean ± SD [range] disease duration = 2.93 ± 2.70 [6 months; 15 years]. The most frequent types of JIA were systemic (33.3%), oligoarticular (30.8%) and polyarticular negative RF (26.9%). Other parameters included positive ANA in 41.0%, positive RF in 7.7% and uveitis in 9.0%. The most frequent treatment was methotrexate (59.0%), followed by biological therapy (47.4%), non-steroid anti-inflammatory drugs (43.6%) and prednisolone (33.3%). Growth data were available for 67 (85.9%) children, and assessments showed 36% cases of break of the growth curve in both height-for-age and weight-for-age percentiles and 31% in weight-for-height percentiles. In all three parameters, there were shifts towards lower percentiles from time of diagnosis to last follow-up, in both males and females. Correlation and regression analysis showed low age at diagnosis and disease duration to be significant predictors for growth retardation severity. Conclusion: One in three children with JIA has growth retardation, the severity of which is predicted by low age at disease onset and long disease duration.

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The pathophysiology of the growth plate in juvenile idiopathic arthritis

Cited by 60 publications

References 132 publications

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

Assessment of left ventricular functions with tissue Doppler, strain and strain rate echocardiography in children with juvenile idiopathic arthritis: An observational study

Growth Pattern in Children with Juvenile Idiopathic Arthritis: A Retrospective Study

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