Abstract
Parathyroid hormone (PTH) exerts potent and diverse effects in bone and cartilage through activation of type 1 PTH receptors (PTH1R) capable of coupling to protein kinase A (PKA) and PKC. We have used macroarrays to identify zinc finger protein butyrate response factor-1 (BRF1) as a novel PTH regulated gene in clonal and normal osteoblasts of human and rodent origin. We further demonstrate that in human osteoblast-like OHS cells, biologically active hPTH(1-84) and hPTH(1-34) stimulate BRF1 mRNA expression in a dose- and time-dependent manner, while the amino-terminally truncated hPTH(3-84) which does not activate PTH1R has no effect. Moreover, using specific stimulators or inhibitors of PKA and PKC activity, the PTH-elicited BRF1 mRNA expression is mediated through the PKA signaling pathway. In mouse calvarial osteoblasts, BRF1 mRNA levels are upregulated by PTH(1-84) and reduced in response to bone morphogenetic protein 2 (BMP-2). Hence, our data showing that BRF1 is expressed in osteoblastic cells and regulated by PTH and BMP-2, suggest an important role for BRF1 in osteoblasts within the molecular network of PTH-dependent bone remodeling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / metabolism
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Animals
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / metabolism*
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Butyrate Response Factor 1
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Cell Line, Tumor
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Cells, Cultured
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Hedgehog Proteins
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Humans
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Immediate-Early Proteins / genetics
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Immediate-Early Proteins / metabolism*
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Mice
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Osteoblasts / cytology
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Osteoblasts / physiology*
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Osteosarcoma / metabolism
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Parathyroid Hormone / metabolism*
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Peptide Fragments / metabolism
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Rats
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Receptor, Parathyroid Hormone, Type 1
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Receptors, Parathyroid Hormone / metabolism
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Trans-Activators / metabolism
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Transforming Growth Factor beta / metabolism*
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Zinc Fingers
Substances
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BMP2 protein, human
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Bmp2 protein, mouse
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Bmp2 protein, rat
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Butyrate Response Factor 1
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DNA-Binding Proteins
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Hedgehog Proteins
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Immediate-Early Proteins
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PTH1R protein, human
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Parathyroid Hormone
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Peptide Fragments
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Receptor, Parathyroid Hormone, Type 1
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Receptors, Parathyroid Hormone
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Trans-Activators
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Transforming Growth Factor beta
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ZFP36L1 protein, human
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8-Bromo Cyclic Adenosine Monophosphate
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Cyclic AMP-Dependent Protein Kinases