Effects of insulin and insulin‐like growth factors I and II on the growth of equine fetal and neonatal chondrocytes

Henson, Frances; Davenport, Celia; Butler, Lynda L.; Morán, Ignasi; Shingleton, W. D.; Jeffcott, L. B.; Schofield, Paul N.

doi:10.1111/j.2042-3306.1997.tb03156.x

Cited by 49 publications

(39 citation statements)

References 57 publications

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“…In particular, IGF-1 has been shown to have potent mitogenic effects on chondrocytes and other articular cells in vitro and in vivo (9), without affecting their differentiated state. Both IGF-1 and IGF-2 act as autocrine differentiation factors for chondrocyte cell lines in vitro (10), and IGF-1 is mitogenic for isolated equine fetal and neonatal chondrocytes in culture (11). IGF-1 promotes the synthesis of large, cartilage-type proteoglycans in a human chondrosarcoma-derived chondrocyte cell line, and moreover, both IGF-1 and IGF-2 stimulate the proliferation of costal chondrocytes of young rabbits.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints

Zhang

Ghivizzani

Lechman

et al. 2000

Arthritis & Rheumatism

105

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Objective. To examine the effect of insulin-like growth factor 1 (IGF-1) on the regulation of cartilage synthesis and other articular events in vivo.Methods. A first-generation adenoviral vector expressing human IGF-1 (AdIGF-1) from the cytomegalovirus promoter was constructed. Particles of AdIGF-1 (5 ؋ 10 9 ) were injected through the patellar tendon into normal rabbit knee joints and rabbit knee joints with antigen-induced arthritis (AIA), with the same dose of a control adenoviral vector injected into the contralateral knees. Lavage fluids were obtained from rabbit knee joints on days 3 and 7 postinjection and used for analysis of IGF-1 expression, white blood cell infiltration, and cartilage breakdown. Cartilage chips from rabbit joints were used for assay of new proteoglycan synthesis, and tissues also were harvested from the dissected knees for histologic study.Results. Intraarticular injection of AdIGF-1 resulted in a mean of 180.6 ng/ml of IGF-1 expression in the lavage fluid from rabbit joints. IGF-1 expression stimulated new proteoglycan synthesis in both naive and AIA rabbit knees, but had no significant chondroprotective or antiinflammatory effects. Histologic analysis showed that elevated levels of IGF-1 expression in both normal and arthritic knees had no adverse pathologic effects on synovium or adjacent muscles. Conclusion.Gene transfer of IGF-1 into rabbit knee joints promotes proteoglycan synthesis without significantly affecting inflammation or cartilage breakdown. In addition, no adverse effects following intraarticular IGF-1 gene delivery were observed. Thus, local gene transfer of IGF-1 to joints could serve as a therapeutic strategy to stimulate new matrix synthesis in both rheumatoid arthritis and osteoarthritis.Arthritis-associated and injury-mediated cartilage loss is a significant medical problem with no current effective treatment. In arthritis, both steroidal and nonsteroidal drugs appear to be effective in blocking inflammation and pain, but have only limited efficacy in blocking cartilage degradation. Biologic agents such as inhibitors of tumor necrosis factor ␣ (TNF␣) and interleukin-1 (IL-1) have been shown to inhibit the destructive effects of TNF␣ and IL-1␤ on cartilage, but are unable to enhance chondrocyte metabolism.Growth factors such as the bone morphogenetic proteins (BMP), hedgehog proteins, and transforming growth factor ␤s (TGF␤), as well as insulin-like growth factors (IGF) potentially are able to facilitate chondrogenesis or affect cartilage metabolism (1-8). In particular, IGF-1 has been shown to have potent mitogenic effects on chondrocytes and other articular cells in vitro and in vivo (9), without affecting their differentiated state. Both IGF-1 and IGF-2 act as autocrine differentiation factors for chondrocyte cell lines in vitro (10), and IGF-1 is mitogenic for isolated equine fetal and neonatal chondrocytes in culture (11). IGF-1 promotes the synthesis of large, cartilage-type proteoglycans in a human chondrosarcoma-derived chondrocyte cell line, and moreover,...

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Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints

Zhang

Ghivizzani

Lechman

et al. 2000

Arthritis & Rheumatism

105

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“…Porém, a não regressão das lesões ou aparecimento das anormalidades radiográficas após 5 meses de idade também poderia estar relacionada a concentrações maiores de insulina sérica nos potros PSL entre 7 e 10 meses. Henson et al (1997) sugerem que o papel da insulina é o de aumentar a sobrevivên-cia dos condrócitos ou suprimir sua diferenciação e/ou apoptose na cartilagem de crescimento, diminuindo a velocidade com que as células entram na fase terminal de hipertrofia, e levando ao acúmulo de condrócitos hipertrofiados na cartilagem e à diminuição da velocidade de ossificação endocondral.…”

Section: Glicose Plasmáticaunclassified

“…Dentre eles o fator de crescimento tipo insulina 1 (IGF-I) tem mostrado promover o crescimento e a diferenciação de condrócitos (Henson et al 1997), além de estimula-los a sintetizar constituintes da matriz cartilagínea como colágeno, proteoglicanos e ácido hialurônico (Verwilghen et al 2009b), induzindo o reparo cartilagíneo (Fortier et al 2001). Também foi relatado que o IGF-1 protege os condró-citos da apoptose induzida por diferentes estímulos, inibe os efeitos catabólicos da interleucina-1 sobre a síntese de proteoglicanos, e suprime a degradação dos componentes da matriz cartilagínea reduzindo a expressão e atividade de metaloproteinases 1 e 8 (Lejeune et al 2007).…”

Section: Introductionunclassified

Identificação dos níveis séricos do fator de crescimento tipo insulina 1 em potros com osteocondrose

Baccarin¹,

Pereira²,

Roncati³

et al. 2011

Pesq. Vet. Bras.

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A osteocondrose é uma das doenças ortopédicas do desenvolvimento mais comuns em cavalos, e deve ser encarada como uma desordem multifatorial. Caracteriza-se por ser uma doença dinâmica, onde o processo de reparo inicia-se quase que imediatamente após a formação da lesão osteocondral. A intensidade e eficácia deste reparo são fortemente relacionados à idade, e estão associados a reposição dos componentes da matriz cartilagínea. Uma vez que o fator de crescimento tipo insulina-1 (IGF-1) age regulando o crescimento da cartilagem articular, este estudo objetivou descrever os níveis séricos de IGF-I, insulina e glicose em potros Puro Sangue Lusitano hígidos ou com osteocondrose, desde o nascimento até 18 meses de idade. Dos potros acompanhados, 76,08% apresentaram sinais radiográficos de osteocondrose com um mês de idade, porém somente 16,2% mantiveram as lesões aos 18 meses. As concentrações de IGF-1 alcançaram picos entre 14 e 16 meses, equivalente ao início da puberdade. As concentrações de IGF-1 nos potros com osteocondrose foram menores que potros sadios, aos 2 e 5 meses (P<0,05), e os de insulina aos 2 meses (P<0,05). Em criatórios com alta ocorrência de osteocondrose recomenda-se que as mensurações dos níveis séricos de IGF-1 e insulina ocorram durante os primeiros 6 meses de idade, para que haja tempo hábil de se estabelecer medidas profiláticas e de tratamento.

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“…Hypotheses for the cause of the dyschondroplasia included primary nutritional or hormonal imbalances (insulin). 41,42,104 The study by Henson et al 42 included localization of type VI collagen. Collagens were subsequently studied as a group 113 and in terms of individual types, including type II, 61,62,103 type I, 103 and type X.…”

Section: What Was Known About the Pathogenesis Of Osteochondrosis In mentioning

confidence: 99%

An Update on the Pathogenesis of Osteochondrosis

2015

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Osteochondrosis is defined as a focal disturbance in endochondral ossification. The cartilage superficial to an osteochondrosis lesion can fracture, giving rise to fragments in joints known as osteochondrosis dissecans (OCD). In pigs and horses, it has been confirmed that the disturbance in ossification is the result of failure of the blood supply to epiphyseal growth cartilage and associated ischemic chondronecrosis. The earliest lesion following vascular failure is an area of ischemic chondronecrosis at an intermediate depth of the growth cartilage (osteochondrosis latens) that is detectable ex vivo, indirectly using contrast-enhanced micro-and conventional computed tomography (CT) or directly using adiabatic T1r magnetic resonance imaging. More chronic lesions of ischemic chondronecrosis within the ossification front (osteochondrosis manifesta) are detectable by the same techniques and have also been followed longitudinally in pigs using plain CT. The results confirm that lesions sometimes undergo spontaneous resolution, and in combination, CT and histology observations indicate that this occurs by filling of radiolucent defects with bone from separate centers of endochondral ossification that form superficial to lesions and by phagocytosis and intramembranous ossification of granulation tissue that forms deep to lesions. Research is currently aimed at discovering the cause of the vascular failure in osteochondrosis, and studies of spontaneous lesions suggest that failure is associated with the process of incorporating blood vessels into the advancing ossification front during growth. Experimental studies also show that bacteremia can lead to vascular occlusion. Future challenges are to differentiate between causes of vascular failure and to discover the nature of the heritable predisposition for osteochondrosis.

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Effects of insulin and insulin‐like growth factors I and II on the growth of equine fetal and neonatal chondrocytes

Cited by 49 publications

References 57 publications

Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints

Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints

Identificação dos níveis séricos do fator de crescimento tipo insulina 1 em potros com osteocondrose

An Update on the Pathogenesis of Osteochondrosis

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