2/20/2023 0 Comments Chen jing keAsterisks * and hashtags # indicate significant difference from sham controls and OVX, respectively. The data are expressed mean ± SEM calculated from six mice. MiR-29a compromised the ovariectomy upregulation of RANKL and CXCL12 expression in bone marrow mesenchymal cells ( a). We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3'-UTR of RANKL. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C-X-C motif chemokine ligand 12 (CXCL12) expression. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. MicroRNA is known to regulate tissue remodeling however, its role in the development of osteoporosis remains elusive. Zhao Fei was awarded the 1999 Golden Rooster Award for Best Cinematography.Ĭhen Kaige noted upon the film's premiere at the Cannes Film Festival that he hoped The Emperor and the Assassin would hold relevance to the events of the time, notably the Yugoslav Wars.Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. The Emperor and the Assassin won the Technical Grand Prize at the 1999 Cannes Film Festival and was in competition for the Palme d'Or. He is further saddened when Lady Zhao returns to Qin only to retrieve Jing Ke for burial. The attempt fails, but Ying Zheng expresses his fury when his associates make no attempt to stop the assassin and he is forced to kill Jing Ke himself. After learning of Ying Zheng's massacre of the children in her home state of Zhao, Lady Zhao desires the assassination in earnest. Lady Zhao persuades Jing Ke to perform the assassination. In the film, Ying Zheng sends his concubine Lady Zhao to the Yan state as a spy to enlist a Yan assassin to attempt to assassinate him, intending to use that as a casus belli to start a war against Yan. The first incident is the climax of the film, with earlier scenes foreshadowing it the other two incidents occur between the fictional genesis and historical manifestation of the first. The story consists of three main incidents: the attempt by Jing Ke to assassinate Ying Zheng in 227 BCE the (fictitious) rumour of a Chief Minister's having sired the latter before transferring his concubine to become the Queen Dowager and the story of an official having sired children by the Queen Dowager herself. However, his experiencing of various betrayals and losses slowly turn him into a mad tyrant. He is essentially depicted as an idealist seeking to impose a peace or unity on the world. The film covers much of Ying Zheng's career, recalling his early experiences as a hostage and foreshadowing his dominance over China.
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