Fetal-originated osteoarthritis is relative to poor cartilage quality and may exhibit transgenerational genetic effects. Previous findings revealed prenatal dexamethasone exposure (PDE) induced poor cartilage quality in offspring.This study focused on further exploring molecular mechanism, heritability, and early intervention of fetal-originated osteoarthritis.Pregnant rats (F0) were segregated into control and PDE groups depending upon whether dexamethasone was administered on gestational days (GDs) 9-20. Some female offspring were bred with healthy males during postnatal week (PW) 8 to attain the F2 and F3 generations. The F3-generation rats were administrated with glucosamine intragastrically at PW12 for 6 weeks. The knee cartilages of male and female rats at different time points were harvested to assay their morphologies and functions. Furthermore, primary chondrocytes from the F3-generation rats were isolated to confirm the mechanism and intervention target of glucosamine.Compared with the control, female and male rats in each generation of PDE group showed thinner cartilage thicknesses; shallower and uneven staining; fewer chondrocytes; higher Osteoarthritis Research Society International scores; and lower mRNA and protein expression of SP1, TGFβR1, Smad2, SOX9, ACAN and COL2A1. After F3-generation rats were treated with glucosamine, all of the above changes could be reversed. In primary chondrocytes isolated from the F3-generation rats of PDE group, glucosamine promoted SP1 expression and binding to TGFβR1 promoter to increase the expression of TGFβR1, p-Smad2, SOX9, ACAN and COL2A1, but these were prevented by SB431542 (a potent and selective inhibitor of TGFβR1).PDE induced chondrodysplasia in offspring and stably inherited in F3-generation rats, which was related to decreased expression of SP1/TGFβR1/Smad2/SOX9 pathway to reduce the cartilage matrix synthesis, without major sex-based variations. Glucosamine could alleviate the poor genetic cartilage quality in offspring induced by PDE by up-regulating SP1/TGFβR1 signaling, which was prevented by a TGFβR1 inhibitor. This study elucidated the molecular mechanism and therapeutic target (TGFβR1) of genetic chondrodysplasia caused by PDE, which provides a research basis for precisely treating fetal-originated osteoarthritis.
As a synthetic glucocorticoid, dexamethasone is widely used to treat potential premature delivery and related diseases. Our previous studies have shown that prenatal dexamethasone exposure (PDE) can cause bone dysplasia and susceptibility to osteoporosis in female rat offspring. However, whether the effect of PDE on bone development can be extended to the third generation (F3 generation) and its multigenerational mechanism of inheritance have not been reported. In this study, we found that PDE delayed fetal bone development and reduced adult bone mass in female rat offspring of the F1 generation, and this effect of low bone mass caused by PDE even continued to the F2 and F3 generations. Furthermore, we found that PDE increases the expression of miR-98-3p but decreases JAG1/Notch1 signaling in the bone tissue of female fetal rats. Moreover, the expression changes of miR-98-3p/JAG1/Notch1 caused by PDE continued from the F1 to F3 adult offspring. Furthermore, the expression levels of miR-98-3p in oocytes of the F1 and F2 generations were increased. We also confirmed that dexamethasone upregulates the expression of miR-98-3p in vitro and shows targeted inhibition of JAG1/Notch1 signaling, leading to poor osteogenic differentiation of bone marrow mesenchymal stem cells. In conclusion, maternal dexamethasone exposure caused low bone mass in female rat offspring with a multigenerational inheritance effect, the mechanism of which is related to the inhibition of JAG1/Notch1 signaling caused by the continuous upregulation of miR-98-3p expression in bone tissues transmitted by F2 and F3 oocytes.
Body image dissatisfaction and aggressive behavior have become important public health problem in children and adolescents, and body image dissatisfaction may increase the occurrence of aggressive behavior. The aim of this study was to explore the correlation between body image dissatisfaction and aggressive behavior among Chinese children in different developmental stages.The stratified cluster sampling method was used to effectively survey 518 children aged 8-15 years. The Body Shape Questionnaire and the Buss-Warren Aggressive Questionnaire scale were used to measure body image dissatisfaction and aggressive behavior. Pubertal development stages were divided into three stages according to Tanner criteria.There was a main correlation path of body image dissatisfaction - hostility - anger - indirect aggression - physical aggression in boys with stage I and stage II and in girls with stage I and stage III. In addition, there were direct paths of hostility - indirect aggression, hostility - verbal aggression, anger - physical aggression, and anger - verbal aggression in boys with stage I; hostility - indirect aggression, hostility - verbal aggression, and anger - physical aggression in boys with stage II and in girls with stage I; and anger - physical aggression, and anger - verbal aggression in girls with stage III.Body image dissatisfaction might positively correlate with aggression through hostility among Chinese children and adolescents, and their association paths were different in different puberty stages.
Objective To describe the prevalence of psychosomatic sub-health symptoms and to explore the effects of family factors on them among university students. Methods Based on stratified,convenience cluster sampling,questionnaire investigation was conducted among 3 320 students from 2 universities of Bengbu city,which contained demographic characteristics,family factors and multidimensional sub-health questionnaire of adolescents (MSQA) . χ2 test and Logistic regression analysis were used to examine the risk factors of sub-health symptoms. Results The prevalence of overall sub-health symptoms among students was 46. 0 % . Of the students 30. 0% reported physical symptoms and the rates of physical inactivity,physiological dysfunction,and immunity decline were 27. 0% ,42. 0% and 34. 1% ,respectively. Of the students 36. 5% reported mental symptoms and the rates emotional symptoms,behavioral symptoms and social adaptation problems were 68. 6% ,35. 5% and 85. 8% , respectively. The main family factors influce sub-health symptom were family type and the health status of parents. Conclusion The prevalence rate of sub-health symptoms among university students was very high. The risk factors for sub-health symptoms were single-parent family and lower health level of parents .
Objective
To study the characteristics and correlation of sex hormone levels, blood lipids, and visceral fat area in postmenopausal women with T2DM.
Methods
A total of 258 cases of postmenopausal T2DM were recruited, including 46 cases of menopause for 1-5 years (group A), 49 cases of menopause for 6-10 years (group B), and 163 cases with menopause more than 10 years (C group). The related clinical information of patients was recorded.
Results
Compared among the three groups, there were statistical differences in total cholesterol(F=3.287, P=0.039) and testosterone(Chi-Square=8.324, P=0.016). No significant difference in FSH, LH, estradiol, low density lipoprotein, triglyceride, visceral fat area and subcutaneous fat area(P>0.05) among three groups was observed. After correction of confounding factors, FSH was independently positively related with for total cholesterol and low-density lipoprotein respectively (P=0.006, P=0.009). LH was independently positively related with total cholesterol(P=0.003) and low-density lipoprotein respectively(P=0.003). Estradiol was independently negatively related with total cholesterol(P=0.014) and low-density lipoprotein(P=0.020), respectively. Testosterone was correlated independently with visceral fat area(P=0.008); FSH, LH, estradiol, and testosterone were not correlated to triglyceride and subcutaneous fat area(P>0.05).
Conclusion
(1)In T2DM patients with the increase of postmenopausal time, the total cholesterol increases first, and then decreases; testosterone decreases first, and then increases. (2)In T2DM patients, the total cholesterol and low-density lipoprotein increase with the increase of FSH and LH, increase with the decrease of estradiol, and the area of visceral fat increases with the testosterone together.
Key words:
Diabetes mellitus, type 2; Postmenopausal women; Sex hormones; Blood lipids; Visceral fat area
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)