Potential effect of Enterolactone and Raloxifene in reversing osteoarthritis markers in cultured human articular chondrocytes.

BACKGROUND: Osteoarthritis (OA) is associated with cartilage destruction. Maintenance of differentiated chondrocyte biomarkers is important in prevention of degeneration. Selective estrogen receptor modulators (SERMs) such as raloxifene (Ral) and phytoestrogens like enterolactone (Ent) which have structural and functional homologies with estrogen can mime their action. This study was undertaken to evaluate in vitro the possible effects of Ral and Ent on the expression of differentiated, dedifferentiated and hypertrophic biomarkers in human articular chondrocytes (HAC). METHODS: Chondrocytes of osteoarthritic patients, harvested from one passage cell culture, were treated with Ral (0.1 and 1 µM) and Ent (1 and 5 µM) for 10 and 12 days in two- (2D) and three-dimensional (3D) models. Genes expression of type I collagen (COL1A1), type II collagen (COL2A1), type X collagen (COL10A1), aggrecan (ACAN) and small novel rich in cartilage (SNORC), were detected by real-time PCR and by Western-Blotting. RESULTS: Our study revealed that Ral increased COL2A1, ACAN and SNORC and decreased concomitantly COL1A1 and COL10A1 genes expression when compared to untreated OA chondrocytes. Ent increased COL2A1 and decreased genes expression of the other biomarkers cited above like COL1A1. Our results demonstrated that low doses of 17ß-oestradiol (E2), Ral and Ent had positive effects on the expression of differentiated chondrocyte markers such as COL2A1, ACAN and SNORC whereas high dose of these compounds inhibited their effects. Our results showed that 1µM of Ral induced an up-regulation of COL2A1, ACAN and SNORC expression and a down-regulation of COL1A1 and COL10A1 expression in HAC incubated in 3D for 12 days. CONCLUSIONS: This study showed that SERMs like Ral and a phyto-estrogen like Ent induced the expression of differentiated chondrocyte markers of hyaline cartilage: COL2A1, ACAN and SNORC and decreased COL1A1 and COL10A1 genes expression on HAC of osteoarthritis patients.

Epidemiology of neural tube defect subtypes in Tunisia, 1991-2011.

BACKGROUND: Neural tube defects are common major congenital anomalies that result from very early disruption in the development of the brain and spinal cord. AIM OF THE STUDY: We conducted an epidemiological study to determine the impact of some feto-maternal characteristics in the occurrence of NTD subtypes. METHODS: Characteristics and outcomes of births with NTD and pregnancy characteristics of mothers over a period of twenty years (1991-2011) were recorded in the medical chart. RESULTS: From 1991 through 2011, 769 stillborns with NTD were delivered, yielding a prevalence of 2.02/10,000. The increase in NTD prevalences over these years was statistically significant (P = 0.000). In addition, differences between prevalences of NTD subtypes over season (P = 0.003) and between genders (P < 0.001) were significant. The highest frequency was noticed in winter with 3, 7 per 10,000 births among females. The difference in fetal term between subtypes was significant (P = 0.017). The probability to have a malformed fetus with a weight less than 1500 g was three times higher in myelomeningocele than in craniorachischisis, two times higher in anencephaly and encephalocele, but two times lower than rachischisis. Mothers with one gestation were two fold higher in anencephaly than in encephalocele. Nulliparous mothers' cases were significantly more likely to have NTD than uni- or multiparous mothers. O+ mother's blood type presented a significant risk factor and was significantly less common in myelomeningocele than in rachischisis, but three times higher than in craniorachischisis. Consanguinity was present in cases with rachischisis and was two times higher than in cases with anencephaly, and three times higher than in cases with encephalocele. In this study, the results have been interpreted with caution due to analyses not being adjusted. CONCLUSION: One of the main findings of the study is that there are many differences between NTD subtypes, which suggests that there may be etiologic differences between subtypes. This suggests that, although epidemiologic studies frequently do not distinguish between NTD subtypes in analyses, they should be analyzed separately when possible.