Insulin‐like growth factor 1–induced interleukin‐1 receptor II overrides the activity of interleukin‐1 and controls the homeostasis of the extracellular matrix of cartilage

Abstract

Objective. We examined the effect of the insulinlike growth factor 1 (IGF-1)/IGF receptor I (IGFRI) autocrine/paracrine anabolic pathway on the extracellular matrix (ECM) of human chondrocytes and the mechanism by which IGF-1 reverses the catabolic effects of interleukin-1 (IL-1).Methods. Phenotypically stable human articular cartilage cells were obtained from normal cartilage and maintained in culture in alginate beads for 1 week to reach equilibrium of accumulated cell-associated matrix (CAM) compounds. Levels of CAM components aggrecan and type II collagen ( Conclusion. These findings reveal a new paradigm by which IGF-1 influences chondrocyte metabolism, by reversing the IL-1-mediated catabolic pathway through up-regulation of its decoy receptor.Homeostasis of the extracellular matrix (ECM) of articular cartilage is dependent on the responses of articular cartilage cells to autocrine and paracrine anabolic and catabolic pathways. The most relevant growth factors and cytokines known to be involved in cartilage metabolism are produced by the chondrocytes themselves (1,2) Synthesis and accumulation of the ECM is regulated by locally produced growth factors, such as the insulin-like growth factors (IGFs) and transforming growth factor ␤. A large body of experimental data has substantiated the importance of IGFs 1 and 2 as promoters of growth and matrix synthesis by articular cartilage cells. Both IGFs enhance aggrecan synthesis by human articular cartilage cells cultured in serum-free medium (3,4). The two forms of IGF, however, differentially affect chondrocyte metabolism. It has been suggested that in cartilage, IGF-1 is the regulator of growth and differentiation, whereas IGF-2 may be an important regulator of glucose metabolism (5). IGF-1 has been shown to enhance the synthesis of aggrecan and type II collagen (CII) by chondrocytes (6-9) and to directly decrease both basal and cytokine-stimulated degradation of proteoglycan in cartilage (10). Although it has been proposed that the action of IGF-1 is predominantly as an endocrine factor, whereas IGF-2 interacts Supported by an FWO grant (3G013201). Studies were performed in collaboration with the

The role of insulin-like growth factor-I in hyaluronan mediated repair of cultured cartilage explants

“…We have continued to investigate whether or not the enhanced PG synthesis is due to suppression of catabolic activities or enhancement of anabolic pathways or both. We report here that the enhanced reparative activities are associated with enhanced IGF-1 activity, an activity that contributes in a major way to PG synthesis in cartilage [38] and that also represses PG catabolism by enhancing IL-1 receptor II expression [39].…”

Genetic association analysis of the IGFBP7, ADAMTS3, and IL8 genes as the potential osteoarthritis susceptibility that maps to chromosome 4q

“…Two interesting recent findings are that IGF-I can reverse the interleukin 1 (IL1) mediated destruction of articular cartilage 10 and that increasing concentrations of IGFBPs 3 and 5 can lead to improvements in the OA joint.…”

MEKhANIZMY EMBRIOGENEZA PRI OSTEOARTROZE:ROL' DIFFERENTsIROVKI KhONDROTsITOVV REZORBTsII SUSTAVNOGO KhRYaShchA

“…Кроме того, ИЛ 1β может индуцировать се-крецию ИФР 1 и ИФР-связывающих белков хондроцита-ми, а также увеличивать количество его рецепторов, хотя не влияет на уровень экспрессии РНК ИФР 1 [155]. На-против, ИФР 1 может противодействовать активности ИЛ 1, индуцируя экспрессию растворимого белка ИЛ 1 рецептора 2 [90].…”

“…Про-цесс минерализации в нижнем отделе зоны гипертрофии ростковой пластинки сопровождается экспрессией ос-теокальцина, который является маркером зрелых остео-бластов и, как предполагается, участвует в минерализа-ции хондроцитов, гомеостазе Са 2+ и увеличении экс-прессии ANK (белка анкилозы), который ответствен за транспорт внутриклеточного неорганического фосфата во внеклеточное пространство [89]. Минерализация, ве-роятно, регулируется аннексинами II, V и VI, которые интенсивно экспрессируются в поздне-гипертрофиро-ванных хондроцитах ростковой пластинки и формируют кальциевые каналы, облегчающие формирование пер-вичной минеральной фазы [90]. Кроме того, аннексин V, как оказалось, способен индуцировать экспрессию ан-нексинов II и VI, остеокальцина, Runx2 и ALP, а также стимулировать апоптозную активность в нижнем отделе зоны гипертрофии [75,91]…”