The attenuation of insulin-like growth factor signaling may be responsible for relative reduction in matrix synthesis in degenerated areas of osteoarthritic cartilage

Abstract Background In osteoarthritis (OA), cartilage matrix is lost gradually despite enhanced synthesis by chondrocytes. This paradox may be explained, at least partly, reduced chondrocyte anabolism in degenerated area of OA cartilage. However, to date, it not known why suppressed those areas. Methods Cartilage was obtained from control knees and end-stage macroscopically preserved areas areas, gene expression analyzed respective regions using laser capture microdissection qPCR. For the protein analysis, pairs, proteins were extracted urea buffer. Protein concentrations determined Luminex compared between explants prepared cultured presence or absence an AKT inhibitor, evaluated Finally, SP1 cartilage, significance Sp1 on IGF1R IRS1 investigated experiments primary Results Within IGF-1, IGF-2, while all six IGF-binding genes examined former Consistent results a analysis. explant culture, inhibition signaling abrogated abundant over indicating that ascribed, attenuated IGF signaling. considerably severely which correlated well with IRS1. chondrocytes, induction suppression expression. Conclusions The this study suggest responsible, for