Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

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.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine‐exposed female adult rat offspring

“…PCE can increase the susceptibility to osteoarthritis in adult rat offspring and that its mechanism was related to the accumulation of localized cholesterol in the articular cartilage (43). Taken together, these studies suggest that PCE can induce hypercholesterolemia in adult rat offspring and increase the risk of multiple metabolic diseases (e.g., cardiovascular disease and osteoarthritis).…”

“…Our previous studies have confirmed that with overexposure to maternal GCs induced by PCE, multiple organs of fetal rats appeared to be structurally and functionally different during development. The liver, as one of those important organs, had enhanced TG synthesis (10), whereas secondary organs (e.g., articular cartilage and kidney) exhibited varying degrees of developmental inhibition and dysfunction (43,54). In this study, we confirmed that the liver had enhanced cholesterol synthesis function under high levels of maternal GCs, which is the specific manifestation of the thrifty phenotype in the fetal liver and constitutes the pathophysiological basis of susceptibility to hypercholesterolemia and related metabolic diseases in adult offspring.…”

Caffeine, a Risk Factor for Osteoarthritis and Longitudinal Bone Growth Inhibition

“…Caffeine (1,3,7-trimethylxanthine) is a natural alkaloid belonging to the family of methylxantines [23][24][25][26][27][28][29][30][31]. The main caffeine sources are tea leaves, cola nuts, and coffee and cocoa beans [23][24][25][26][27][28][29][30][31][32].…”

“…Nonetheless, it is among the most frequently consumed substances, with an average daily ingestion of 120 mg [23][24][25][26][27][28][29][30][31][32]. It is present in beverages (e.g., coffee, tea, soft drinks, and energy drinks), food (e.g., cocoa and chocolate) [23][24][25][26][27][28][29][30][31][32], and some stimulants and is used as an adjuvant to increase the absorption of some medications [23][24][25][26][27][28][29][30][31]. Studies show that coffee (60%-75%) and tea (15%-30%) are the main sources of caffeine for adults, while among children, chocolate and soft drinks are the major intake sources [30][31][32] (Figure 3).…”

“…It is well-known that in adults, chronic and elevated caffeine intake above 500-600 mg/day (equivalent to four or seven cups of coffee) can cause multiple symptoms, including nervousness, irritability, insomnia, arrhythmias, increased diuresis, tachypnoea, gastrointestinal disturbances, hypercalciuria, female infertility, and an increased risk of osteoporosis and hip fracture [30,31]. In addition to these effects, multiple in vitro and in vivo experiments suggest that caffeine overconsumption could be harmful to the musculoskeletal system, including the hyaline cartilage [23][24][25][26]34,[42][43][44] (Figure 3).…”