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Regulation of BMP‐7 expression by retinoic acid and prostaglandin E 2
Author(s) -
Paralkar V.M.,
Grasser W.A.,
Mansolf A.L.,
Baumann A.P.,
Owen T.A.,
Smock S.L.,
Martinovic S.,
Borovecki F.,
Vukicevic S.,
Ke H.Z.,
Thompson D.D.
Publication year - 2002
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/jcp.10048
Subject(s) - retinoic acid , retinoic acid inducible orphan g protein coupled receptor , chemistry , microbiology and biotechnology , prostaglandin , expression (computer science) , bone morphogenetic protein 2 , retinoic acid receptor gamma , biochemistry , biology , retinoic acid receptor , computer science , gene , in vitro , programming language
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor‐beta (TGF‐β) gene superfamily of growth and differentiation factors. Members of the BMP family were originally cloned and characterized by their ability to induce ectopic bone formation. Of the various BMPs cloned, the bone inductive ability of BMP‐7 (OP‐1) and BMP‐2 has been well characterized. Both BMP‐7 and ‐2 have been shown to have clinical utility in the healing of non‐union fractures. However, in spite of the various advances in BMP research, the physiological regulation of BMPs is not well understood. Here we studied the expression of BMP‐7 by cloning a 4.6‐kB fragment of the human BMP‐7 promoter (hBMP‐7p) and placing it upstream of a luciferase reporter. The promoter reporter construct was stably transfected into different cell backgrounds and its regulation by various factors was investigated. We show that retinoic acid (RA) treatment results in an upregulation of the hBMP‐7p reporter activity. This regulation of the hBMP‐7p was further confirmed by Northern blot, PCR, and Western blot analyses, which showed an increase in both BMP‐7 mRNA and protein expression upon treatment with RA. We further show that RA specifically upregulates expression of osteocalcin via activation of BMP‐7 mRNA and protein in vitro. Similarly, prostaglandin E 2 (PGE 2 ) treatment increases BMP‐7 mRNA and protein levels, but does not transcriptionally activate the hBMP‐7p. Additionally, in vivo expression of BMP‐7 in bone was increased upon PGE 2 treatment. In conclusion, RA and PGE 2 upregulate BMP‐7 protein expression both in vitro and in vivo. J. Cell. Physiol. 190: 207–217, 2002. © 2002 Wiley‐Liss, Inc.