Recruitment of a Prostaglandin E Receptor Subtype, EP3-Expressing Bone Marrow Cells Is Crucial in Wound-Induced Angiogenesis

Prostaglandin E2(PGE2) is an anabolic agent in vivo that stimulates bone formation by recruiting osteoblasts from bone marrow precursors. To understand which of the known PGE2 receptors (EP1–4) is involved in this process, we tested the effect of PGE2 and various EP agonists and/or antagonists on osteoblastic differentiation in cultures of bone marrow cells by counting bone nodules and measuring alkaline phosphatase activity. PGE2increased both parameters, peaking at 100 nM, an effect that was mimicked by forskolin and was abolished by 2′,3′-dideoxyadenosine (an adenylate cyclase inhibitor) and was thus cAMP dependent, pointing to the involvement of EP2 or EP4. Consistently, 17-phenyl-ω-trinor PGE2(EP1 agonist) and sulprostone (EP3/EP1agonist) lacked any anabolic activity. Furthermore, butaprost (EP2 agonist) was inactive, 11-deoxy-PGE1(EP4/EP2agonist) was as effective as PGE2, and the PGE2 effect was abolished dose dependently by the selective EP4 antagonist AH-23848B, suggesting the involvement of EP4. We also found that PGE2 increased nodule formation and AP activity when added for the initial attachment period of 24 h only. Thus this study shows that PGE2 stimulates osteoblastic differentiation in bone marrow cultures, probably by activating the EP4 receptor, and that this effect may involve recruitment of noncommitted (nonadherent) osteogenic precursors, in agreement with its suggested mode of operation in vivo.

Download Full-text

PGE2 Activates Cementoclastogenesis by Cementoblasts via EP4

Journal of Dental Research ◽

10.1177/154405910708601011 ◽

2007 ◽

Vol 86 (10) ◽

pp. 974-979 ◽

Cited By ~ 27

Author(s):

H. Oka ◽

M. Miyauchi ◽

K. Sakamoto ◽

S. Moriwaki ◽

S. Niida ◽

...

Keyword(s):

Bone Marrow ◽

Mrna Expression ◽

Cell Line ◽

Alveolar Bone ◽

Bone Marrow Cells ◽

Prostaglandin E ◽

Receptor Subtypes ◽

Mrna Levels ◽

Marrow Cells

Destruction of cementum and alveolar bone is the main causative event for the exfoliation of teeth as a consequence of periodontitis. Prostaglandin E2 (PGE2) and PGE receptor subtypes (EPs) play an important role in modulating osteoblast-mediated osteoclastogenesis; however, no information is available on the role of PGE2 and EPs in regulating cementoblast-mediated cementoclastogenesis. We hypothesized that the PGE2-EPs pathway also regulates cementoblasts’ ability to activate cementoclasts. For these studies, OCCM-30 cells (a mouse cementoblast cell line) were exposed to PGE2 and specific EP agonists. PGE2 (100 ng/mL) and EP4 agonist (1 μM) up-regulated RANKL and IL-6 mRNA levels, while they down-regulated OPG mRNA expression. The EP4 antagonist (1 μM) eliminated these effects of PGE2. PGE2 treatment of co-cultures of OCCM-30 cells with bone marrow cells induced TRAP-positive cells via the EP4 pathway. These findings suggest that PGE2 promotes cementoblast-mediated cementoclastogenesis by regulating the expression of RANKL and OPG via the EP4 pathway.

Download Full-text

Induction of Osteoclastogenesis and Matrix Metalloproteinase Expression by the Lipooligosaccharide of Treponema denticola

Infection and Immunity ◽

10.1128/iai.71.1.226-233.2003 ◽

2003 ◽

Vol 71 (1) ◽

pp. 226-233 ◽

Cited By ~ 33

Author(s):

Bong-Kyu Choi ◽

Hyun Jung Lee ◽

Jung Hwa Kang ◽

Gook Jin Jeong ◽

Cheon Ki Min ◽

...

Keyword(s):

Bone Marrow ◽

Mrna Expression ◽

Alveolar Bone ◽

Bone Marrow Cells ◽

Bone Destruction ◽

Prostaglandin E ◽

Treponema Denticola ◽

Dependent Manner ◽

Mouse Calvaria ◽

Marrow Cells

ABSTRACT Alveolar bone destruction is a characteristic feature of periodontitis. Treponema denticola is known to be involved in periodontitis. To elucidate the role of T. denticola in alveolar bone destruction in periodontitis, the effects of lipooligosaccharide (LOS) from T. denticola on osteoclast formation and on expression of osteoclast differentiation factor (ODF) and osteoprotegerin (OPG) mRNAs were examined in a coculture system by using mouse calvaria and bone marrow cells. In addition, the effect of T. denticola LOS on expression of matrix metalloproteinases (MMPs), which are involved in bone resorption, was estimated in mouse calvaria-derived osteoblastic cells. When the mouse calvaria and bone marrow cells were challenged with LOS (0.1 to 10 μg/ml) for 4 days, the number of tartrate-resistant acid phosphatase-positive multinucleated cells increased in a dose-dependent manner. The expression of ODF mRNA increased, while OPG mRNA expression decreased. Polymyxin B changed the effect of LOS (10 μg/ml) on ODF and OPG mRNA expression to the control level. LOS (10 μg/ml) stimulated prostaglandin E2 (PGE2) production in the cocultures. Adding indomethacin, an inhibitor of prostaglandin synthesis, resulted in a reduction in the number of osteoclasts induced by LOS and eliminated the effect of T. denticola LOS on ODF and OPG mRNA expression. T. denticola LOS increased the levels of mRNAs encoding MMP-3, -8, -9, -10, -13, and -14. Expression of one of these mRNAs, MMP-9 mRNA, was significantly induced by T. denticola LOS. These findings suggest that LOS from T. denticola stimulates osteoclastogenesis and MMP expression. Up-regulation of ODF and down-regulation of OPG by a PGE2-dependent mechanism were involved in the osteoclastogenesis induced by T. denticola LOS.

Download Full-text