Signaling by bone morphogenetic proteins (Bmps) plays a pivotal role in developmental and pathological processes, and is regulated by a complex interplay with secreted Bmp binding factors, including Crossveinless 2 (Cvl2). Although structurally related to the Bmp antagonist Chordin, Crossveinless 2 has been described to be both a Bmp agonist and antagonist. Here, we present the first loss-of-function study of a vertebrate cvl2 homologue, showing that zebrafish cvl2 is required in a positive feedback loop to promote Bmp signaling during embryonic dorsoventral patterning. In vivo, Cvl2 protein undergoes proteolytic cleavage and this cleavage converts Cvl2 from an anti-to a pro-Bmp factor. Embryonic epistasis analyses and protein interaction assays indicate that the pro-Bmp function of Cvl2 is partly accomplished by competing with Chordin for binding to Bmps. Studies in cell culture and embryos further suggest that the anti-Bmp effect of uncleaved Cvl2 is due to its association with the extracellular matrix, which is not found for cleaved Cvl2. Our data identify Cvl2 as an essential pro-Bmp factor during zebrafish embryogenesis, emphasizing the functional diversity of Bmp binding CR-domain proteins. Differential proteolytic processing as a mode of regulation might account for anti-Bmp effects in other contexts.
Purpose This study aimed to describe the epidemiologic characteristics of fracture in the elderly during the COVID-19. Methods This was a retrospective multi-centre study, which included patients who sustained fractures between 20 January and 19 February 2020. The collected data included patients' demographics (age and gender), injury-related (injury type, fracture location, injury mechanism, places where fracture occurred), and treatment modality. SPSS 23.0 was used to describe the data and perform some analysis. Results A total of 436 patients with 453 fractures were included; there were 153 males and 283 females, with an average age of 76.2 years (standard deviation, SD, 7.7 years; 65 to 105). For either males or females, 70-74 years was the most commonly involved age group. A total of 317 (72.7%) patients had their fractures occurring at home. Among 453 fractures, there were 264 (58.3%) hip fractures, accounting for 58.3%. Fall from standing height was the most common cause of fracture, making a proportion of 89.4% (405/453). Most fractures (95.8%, 434/453) were treated surgically, and 4.2% (19/453) were treated by plaster fixation or traction. Open reduction and internal fixation (ORIF) was the most used surgical method, taking a proportion of 49.2% (223/453).
Osterix (Osx) is an essential transcription factor for osteoblast differentiation and bone formation. However, the knowledge of the regulation of Osx expression is poor. MicroRNAs (miRNAs), a class of small non-coding RNAs, play critical roles in numerous biological processes, including the proliferation, differentiation, and survival of cells and organisms. Herein, we aimed to explore the effect of miR-143 on Osx expression and osteogenic differentiation. miR-143, which was suppressor of the osteogenic differentiation of MC3T3-E1 cells, had decreased levels of expression during osteogenic differentiation. Moreover, Osx was identified to be a direct target of miR-143. Inhibition of Osx performed similar effect with miR-143 on osteogenic differentiation, while overexpression of Osx could partially reverse the suppressive effect of miR-143. Collectively, these data indicate that miR-143 is a novel regulator of Osx, and it might play an essential role in the regulation of osteogenic differentiation.
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