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Bone morphogenetic protein‐4 regulates its own expression in cultured osteoblasts
Author(s) -
Pereira Renata C.,
Rydziel Sheila,
Canalis Ernesto
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(200002)182:2<239::aid-jcp13>3.0.co;2-w
Subject(s) - noggin , microbiology and biotechnology , bone morphogenetic protein , bone morphogenetic protein 2 , bmpr2 , bone morphogenetic protein 7 , osteoblast , autocrine signalling , growth factor , chemistry , bone morphogenetic protein 4 , biology , mesenchymal stem cell , progenitor cell , medicine , follistatin , endocrinology , stem cell , cell culture , in vitro , gene , biochemistry , genetics , receptor
During development, bone morphogenetic proteins (BMPs) induce the differentiation of mesenchymal progenitor cells to enter into the osteoblastic lineage, and BMPs enhance osteoblastic function. BMPs and noggin, a specific binding protein that blocks BMP actions, are expressed by osteoblastic cells but there is limited information about regulation of BMP synthesis in skeletal cells. We tested for the expression and regulation of BMP‐4 in cultures of osteoblast‐enriched cells from 22‐day fetal rat calvariae (Ob cells). BMP‐4 caused a short‐lived increase in BMP‐4 mRNA followed by a marked inhibition of BMP‐4 expression. The stimulatory effect was transcriptional, as determined by nuclear run‐on assays, whereas the inhibitory effect was transcriptional and posttranscriptional, because longer BMP‐4 exposure decreased its rate of transcription and shortened the half‐life of BMP‐4 mRNA in transcriptionally arrested Ob cells. BMP‐2 and BMP‐6 also inhibited BMP‐4 mRNA levels. Transforming growth factor β1 increased, whereas fibroblast growth factor‐2, platelet‐derived growth factor BB, and insulin‐like growth factor I decreased BMP‐4 mRNA in Ob cells. BMP‐2 also was expressed by Ob cells and it was downregulated by BMP‐2, BMP‐4, and BMP‐6. Noggin increased BMP‐4 transcripts, suggesting autocrine control of BMP‐4 expression. In conclusion, BMP‐4 inhibits its own expression in Ob cells, a mechanism to limit BMP availability to osteoblasts. J. Cell. Physiol. 182:239–246, 2000. © 2000 Wiley‐Liss, Inc.