Big endothelin changes the cellular miRNA environment in TMOb osteoblasts and increases mineralization

Autor:	Michael G. Johnson, Jasmin Kristianto, Baozhi Yuan, Kathryn Konicke, Robert D. Blank
Rok vydání:	2014
Předmět:	medicine.medical_specialty Endothelin converting enzyme 1 Biology Biochemistry Mineralization (biology) Article chemistry.chemical_compound Calcification Physiologic Rheumatology Osteogenesis Internal medicine microRNA medicine Humans Orthopedics and Sports Medicine education Molecular Biology Gene Cells Cultured education.field_of_study Growth medium Osteoblasts Endothelin-1 Cell Differentiation Biological activity Cell Biology Cell biology MicroRNAs Endocrinology chemistry Bone Morphogenetic Proteins Sclerostin Endothelin receptor Signal Transduction
Zdroj:	Connective Tissue Research. 55:113-116
ISSN:	1607-8438 0300-8207
Popis:	Endothelin (ET1) promotes the growth of osteoblastic breast and prostate cancer metastases. Conversion of big ET1 to mature ET1, catalyzed primarily by endothelin converting enzyme 1 (ECE1), is necessary for ET1's biological activity. We previously identified the Ece1, locus as a positional candidate gene for a pleiotropic quantitative trait locus affecting femoral size, shape, mineralization, and biomechanical performance.We exposed TMOb osteoblasts continuously to 25 ng/ml big ET1. Cells were grown for 6 days in growth medium and then switched to mineralization medium for an additional 15 days with or without big ET1, by which time the TMOb cells form mineralized nodules. We quantified mineralization by alizarin red staining and analyzed levels of miRNAs known to affect osteogenesis. Micro RNA 126-3p was identified by search as a potential regulator of sclerostin (SOST) translation.TMOb cells exposed to big ET1 showed greater mineralization than control cells. Big ET1 repressed miRNAs targeting transcripts of osteogenic proteins. Big ET1 increased expression of miRNAs that target transcripts of proteins that inhibit osteogenesis. Big ET1 increased expression of 126-3p 121-fold versus control. To begin to assess the effect of big ET1 on SOST production we analyzed both SOST transcription and protein production with and without the presence of big ET1 demonstrating that transcription and translation were uncoupled.Our data show that big ET1 signaling promotes mineralization. Moreover, the results suggest that big ET1's osteogenic effects are potentially mediated through changes in miRNA expression, a previously unrecognized big ET1 osteogenic mechanism.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d84ef9c863b9ddbaf4edf858a263fbb https://doi.org/10.3109/03008207.2014.923866 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.