Differential expression of IGF1, IGFR1 and IGFBP3 in mandibular condylar cartilage between male and female rats applied with malocclusion

Abstract

This study was designed to investigate the expression differences of insulin-like growth factor-1 (IGF1), IGF type 1 receptor (IGFR1) and IGF-binding protein-3 (IGFBP3) in mandibular condylar cartilage between male and female rats with experimentally created malocclusion. A total of 40 male and 40 female rats were used, and malocclusion was created by moving the first molars mesially and the third molars distally in the experimental group. Animals were killed at the end of the second and fourth weeks. Haematoxylin and eosin (HE) staining was performed to monitor the changes in cartilage morphology and thickness. Immunohistochemistry and real-time PCR were used to detect the expression of IGF1, IGFR1 and IGFBP3. Osteoarthritis (OA)-like changes were observed in the experimental groups, with 2-week females showing larger OA-like regions than 2-week males (P < 0·05). Compared to their age- and sex-matched controls, both 2- and 4-week males in the experimental groups displayed increased cartilage thickness in the posterior regions (P < 0·05). Compared to their age- and sex-matched controls, the expression of IGF1 was lower in 2-week female group (P < 0·05), but higher in 4-week female, 2- and 4-week male experimental groups (P < 0.05). Similarly, the expression of IGFR1 was lower in 2-week female experimental group (P < 0.05), but higher in 2-week male experimental group (P < 0.05). The higher expression of IGFBP3 was observed in 2-week female, 2- and 4-week male experimental groups (P < 0·05). These results indicate that condylar cartilage from male and female rats respond differently to the malocclusion in early stage of OA, with more serious degeneration in females.

MiR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1, IGF1R and BCL2

“…They suggested that IGF1 stimulates metatarsal longitudinal growth by increasing the proportion of proliferating cells in proliferative zone and enhancing of cell differentiation/hypertrophy in hypertrophic zone 29 . Likewise, during the process of cartilage degeneration, the expression of IGF1and IGF1R decreased in proliferative and hypertrophic zones in female SpragueeDawley rats 30 . BCL2, as a predominant antiapoptotic factor, was frequently used as a maker of cell survival by blocking apoptosis 9 .…”

Women with Osteoarthritis have Elevated Synovial Fluid Levels of Insulin-Like Growth Factor (IGF)-1 and IGF-Binding Protein-3

“…This suggests that although IGF-1 is more abundant in OA, it may not be bioavailable to exert its beneficial effects on cartilage. [16,31] Furthermore, increased local production of IGFBP-3 has been found in OA joints, [32] thus, further limiting the action of IGF-1 during the progression of the disease. [18] Development of treatment strategies that would either increase the levels of bioavailable IGF-1 and/or decrease the local production of IGF-binding proteins may be beneficial to restore homeostasis in OA.…”

A general mechanism for conditional expression of exaggerated sexually‐selected traits

“…Artificially reducing circulating levels of IGF in transgenic mice causes a 30% reduction in body size compared to control littermates . Studies in a broader range of species show circulating IGF levels correlating positively with growth differences, including dog breeds , rats , several species of fish , as well as snakes , ducks , and humans .…”