Abstract
Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway.
Highlights
Between low birth weight and lumbar spine OA8
Through the analysis of repeated measures, the results showed that the body weights of the prenatal caffeine exposure (PCE) group were lower than those of the control group (P < 0 .05)
> 300 mg/d (> 4.3 mg/kg.d)[30,31], which is associated with an increased risk for small for gestational age according to the World Health Organization (WHO)[32]
Summary
Between low birth weight and lumbar spine OA8 Together, these reports indicate that changes to cartilage during intrauterine development may increase susceptibility to OA9. The underlying mechanisms of fetal-origin OA may include cholesterol accumulation in cartilage, which maybe induced by hypercholesteremia. Our previous studies showed that prenatal caffeine exposure (PCE) could elevate the maternal serum glucocorticoid (GC) concentration and over-expose the fetus to maternal GC18–20, resulting in retardation of chondrogenesis by down-regulation of insulin-like growth factor[1] (IGF1) signaling pathway in fetal growth plate cartilage[21]. No studies have addressed whether PCE induces a poor quality of cartilage in adult offspring and whether this poor quality cartilage may be derived from cholesterol accumulation and changes in intrauterine metabolic programming. We investigated the fetal origin mechanisms related to both cholesterol influx (hypercholesteremia) and efflux in articular cartilage.
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