Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone marrow stroma cells.
The recently cloned osteoclastogenesis inhibitory factor, or osteoprotegerin (OPG), has been shown to be a potent inhibitor of osteoclast formation. The inhibition is believed to be mediated through specific binding of OPG to a cell surface ligand on osteoblastic stromal cells. In this report we have studied the effect of the bone resorbing agent prostaglandin E2 (PGE2) on OPG mRNA levels in primary cultures of human bone marrow stroma cells (hBMSC). PGE2 dose- and time-dependently down-regulated the mRNA levels of OPG, as measured by RNAse protection assay. After 4 hours of stimulation with 1 microM PGE2, OPG mRNA levels were significantly decreased. The inhibitory effect was seen at and above 1 nM of PGE2. To elucidate whether the OPG mRNA levels are regulated via the proteinkinase A and/or the proteinkinase C pathways we stimulated cells with either forskolin (FSK) or phorbolic ester (PDbu) respectively. FSK (10 microM) decreased OPG mRNA levels to 50 % of control, whereas PE (10 nM) upregulated the mRNA levels to 250 % of control. These data show that PGE2 down-regulates the expression of OPG mRNA in hBMSC, probably via an increase in cAMP. This mechanism might be involved in PGE2-induced bone resorption.
Brändström
H
H
Department of Internal Medicine, University of Uppsala, Uppsala, S-751 85, Sweden.
Jonsson
K B
KB
Ohlsson
C
C
Vidal
O
O
Ljunghall
S
S
Ljunggren
O
O
D001483:Base Sequence; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism*; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001862:Bone Resorption / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D015232:Dinoprostone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D053244:Osteoprotegerin; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D017931:DNA Primers; D006023:Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D015232:Dinoprostone