1.
NEAT1 functions as a key mediator of BMP2 to promote osteogenic differentiation of renal interstitial fibroblasts.
Zhu, Z, Zhang, X, Jiang, Y, Ruan, S, Huang, F, Zeng, H, Liu, M, Xia, W, Zeng, F, Chen, J, et al
Epigenomics. 2021;(15):1171-1186
Abstract
Aim: To clarify the mechanism of NEAT1, an aberrantly upregulated lncRNA in Randall's plaques (RP) similar to biomineralization, in mediating osteogenic differentiation of human renal interstitial fibroblasts. Materials & methods: A comprehensive strategy of bioinformatic analysis and experimental verification was performed. Results:BMP2 silence abolished the osteogenic differentiation of human renal interstitial fibroblasts promoted by NEAT1. Mechanically, NEAT1 not only induced the nucleolar translocation of EGR1 binding to BMP2 promotor, but also functioned as a sponge of miR-129-5p in the cytoplasm to promote BMP2 expression. Moreover, there was a positive correlation between NEAT1 and BMP2 expression in RP instead of normal renal papilla. Conclusion:NEAT1 acted as a key mediator of BMP2 to promote human renal interstitial fibroblast osteogenic differentiation, through which NEAT1 might be involved in RP formation.
2.
Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy.
Dobnig, H, Sipos, A, Jiang, Y, Fahrleitner-Pammer, A, Ste-Marie, LG, Gallagher, JC, Pavo, I, Wang, J, Eriksen, EF
The Journal of clinical endocrinology and metabolism. 2005;(7):3970-7
Abstract
CONTEXT Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. OBJECTIVE The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. DESIGN This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. SETTING The trial was conducted at 11 clinical study sites. PATIENTS Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. INTERVENTIONS Once-daily sc injections of either placebo or teriparatide (20 or 40 microg) were administered. MAIN OUTCOME MEASURES The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. RESULTS U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P < 0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P < 0.05), and BV/TV (r = 0.54; P < 0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P < 0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. CONCLUSIONS Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.