ERα/ß/DMP1 axis promotes trans-differentiation of chondrocytes to bone cells through GSK-3ß/ß-catenin pathway.

Estrogen-induced premature closing of the growth plate in the long bones is a major cause of short stature after premature puberty. Recent studies have found that chondrocytes can directly trans-differentiate into osteoblasts in the process of endochondral bone formation, which indicates that cartilage formation and osteogenesis may be a continuous biological process. However, whether estrogen promotes the direct trans-differentiation of chondrocytes into osteoblasts remains largely unknown. Chondrocytes were treated with different concentrations of 17ß-estradiol, and Alizarin Red staining and alkaline phosphatase activity assay were used to detected osteogenesis. Specific short hairpin RNA and tamoxifen were used to block the estrogen receptor (ER) pathway and osteogenic marker genes and downstream gene expression were detected using real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining. The findings showed that 17ß-estradiol promoted the chondrocyte osteogenesis in vitro, even at high concentrations. In addition, blocking of the ERα/ß pathway inhibited the trans-differentiation of chondrocytes into osteogenic cells. Furthermore, we found that dentin matrix protein 1 (DMP1), which is a direct downstream molecular of ER, was involved in 17ß-estradiol/ER pathway-regulated osteogenesis. As well, glycogen synthase kinase-3 beta (GSK-3ß)/ß-catenin signal pathway also participates in ERα/ß/DMP1-regulated chondrocyte osteogenesis. The GSK-3ß/ß-catenin signal pathway was involved in ERα/ß/DMP1-regulated chondrocyte osteogenesis. These findings suggest that ER/DMP1/GSK-3ß/ß-catenin plays a vital role in estrogen regulation of chondrocyte osteogenesis and provide a therapeutic target for short stature caused by epiphyseal fusion.

A diagnostic model of idiopathic central precocious puberty based on transrectal pelvic ultrasound and basal gonadotropin levels.

OBJECTIVE: To establish a diagnostic model of idiopathic central precocious puberty on the basis of transrectal pelvic ultrasound and basal gonadotropin. METHODS: A total of 669 girls with Tanner breast development stage II were enrolled in this study from January 2015 to December 2018. The participants were divided into the ICPP group and the premature thelarche group. We analyzed various variables, including age at initial diagnosis, basal luteinizing hormone levels, the long diameter of the uterus, the transverse diameter of the uterus, the anterior-posterior diameter of the uterus, the volume of the uterus, maximum ovarian diameter, average ovarian volume, maximum ovarian volume, number of follicles (≥4 mm), maximum follicular diameter, endometrial thickness, and vaginal wall thickness. RESULTS: The following diagnostic model was established: Y=-14.123 + 0.630 × age at initial diagnosis + 1.119 × transverse diameter of the uterus + 1.278 × anterior-posterior diameter of the uterus + 0.637 × average ovarian volume + 1.316 × maximum ovarian diameter + 0.146 ×number of follicles ≥4 mm + 2.925 × endometrial thickness + 0.559 × basal luteinizing hormone value. The area under curve was 0.922, sensitivity was 84.9%, and specificity was 86.2%. CONCLUSION: Basal LH levels and transrectal pelvic ultrasound should be applied together to improve the accuracy of diagnosis in ICPP.

Methylmalonic Acidemia Complicated by Homocystinuria Diseases: a Report of Three Cases.

This study aims to improve our understanding of methylmalonic acidemia (MMA) complicated by homocystinuria disease by analyzing the clinical characteristics, treatment response and prognosis of three patients. Hyperhomocysteinemia and developmental retardation were present in all patients, epilepsy was present in one patient, and hemolytic uremic syndrome was present in one patient. The conditions of two patients were complicated by pulmonary arterial hypertension, one patient by left pulmonary vein ectopic drainage to the coronary sinus and the other by noncompaction of the ventricular myocardium. The two MMA patients with the complication of severe pulmonary arterial hypertension died because of late diagnosis and irregular treatment of MMA. Echocardiography is necessary for patients with combined MMA and homocystinuria, and these patients are susceptible to cardiovascular disease. When a patient with combined MMA and homocystinuria has the complication of severe pulmonary arterial hypertension, the prognosis is poor.

[Dexamethasone up-regulates the expression of glucocorticoid receptor in growth plate and inhibits the longitudinal growth of bone: experiment with rats].

OBJECTIVE: To investigate the regulation of the glucocorticoid of pharmacological doses on the expression of glucocorticoid receptor in growth plate and to explore the mechanism of the direct inhibition of the longitudinal growth of bone by dexamethasone. METHODS: Twenty 3-week-old male weanling SD rats were randomly divided into two groups: dexamethasone group (n = 12), intraperitoneally injected with dexamethasone 200 microg/100 g body weight once a day for 10 days and control group (n = 8), intraperitoneally injected with normal saline of the same volume. Ten days later the rats were killed. The length of the proximal tibia was excised, fixed and decalcified, and then paraffin embedded. Sections of 5 microm thick were cut and processed for histomorphometry The total height of growth plate, height of proliferative zone, and height of hypertrophic zone were determined. RESULTS: The length of tibia, total height of growth plate, height of proliferative zone, and height of hypertrophic zone of the dexamethasone group were 28.9 mm +/- 1.2 mm, 4.01 microm +/- 0.28 microm, 1.98 microm +/- 0.13 microm, and 1.67 microm +/- 0.18 microm respectively, all significantly lower those of the control group (30.5 mm +/- 1.1 mm, 5.53 microm +/- 0.46 microm, 2.25 microm +/- 0.30 microm, and 2.87 microm +/- 0.19 microm respectively, all P < 0.01). The resting chondrocytes and hypertrophic chondrocytes in the growth plates of the rats in the dexamethasone group all expressed glucocorticoid receptor, whereas the proliferating chondrocytes didn't. The absorbance values of the resting chondrocytes and hypertrophic chondrocytes in the growth plates of the dexamethasone group were 0.238 +/- 0.026 and 0.283 +/- 0.042 respectively, both significantly higher than those of the control group (0.187 +/- 0.027 and 0.211 +/- 0.022 respectively, both P < 0.01). CONCLUSION: The glucocorticoid receptors are essential for the longitudinal growth of bone. The glucocorticoid of pharmacological dose inhibits the longitudinal growth of bone by up-regulating the expression of glucocorticoid receptor.