Prostaglandin E2 Strongly Inhibits Human Osteoclast Formation

Take, Ikuko; Kobayashi, Yasuhiro; Yamamoto, Yohei; Tsuboi, Hideki; Ochi, Takahiro; Uematsu, Setsuko; Okafuji, Norimasa; Kurihara, Saburo; Udagawa, Nobuyuki; Takahashi, Naoyuki

doi:10.1210/en.2005-0451

Cited by 79 publications

(68 citation statements)

References 36 publications

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“…In addition, previous data [2] also showed that PGE 2 strongly inhibits bone resorption. This concurs with the data of Take et al [38] which demonstrate that PGE 2 could act directly as an inhibitor of osteoclastogenesis by its interaction on osteoclast precursors, and of Raisz et al [39] which showed that high concentrations of PGE 2 favour bone deposition, as well as others showing that high levels of PGE 2 induce collagen type I production in OA human osteoblasts [40] and IGF-1 [12] synthesis. However, although RANKL-independent mechanisms are involved in the control of bone remodelling, RANKL-dependent modulation remains the major pathway involved in such remodelling.…”

Section: Discussionsupporting

confidence: 91%

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Tat

Pelletier

Lajeunesse

et al. 2008

Bone

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Background-Osteoarthritis (OA) is the most common human joint disease. Recent studies suggest that an abnormal subchondral bone metabolism is intimately involved in the genesis of this disease. Bone remodelling is tightly regulated by a molecular triad composed of OPG/RANK/ RANKL. RANKL exists as 3 isoforms: RANKL1, 2, and 3. RANKL1 and 2 enhance osteoclastogenesis whereas RANKL3 inhibits this phenomenon. We previously reported that human OA subchondral bone osteoblasts can be discriminated into two subgroups according to their level of PGE 2 [low (L) or high (H)]. Moreover, we also showed that L-OA osteoblasts express higher levels of total RANKL compared to H-OA osteoblasts. In this study, we investigated the level of membranous RANKL, comparing L-and H-OA subchondral bone osteoblasts, as well as its modulation by osteotropic factors. The impact of the modulation of RANKL1 and 3 on the membranous RANKL level was also studied.

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Section: Discussionsupporting

confidence: 91%

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Tat

Pelletier

Lajeunesse

et al. 2008

Bone

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“…Daggers indicate a significant difference between the PSL-treated and untreated OP cells ( osteoclastogenesis from BM cell cultures. This suggests that PSLs also affect the functions of osteoblasts and stromal cells in a paracrine manner because they have receptors for both TGF-b1 and PGE 2 (45,46). PSLs activate p44/p42 ERK but not p38 MAPK in primary cultured rat microglia (16) and macrophages (15).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss

Mei

Kukita

et al. 2010

The Journal of Immunology

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Liposomes containing phosphatidylserine (PS) are engulfed by phagocytes including macrophages, microglia, and dendritic cells. PS liposomes (PSLs) mimic the effects of apoptotic cells on these phagocytes to induce the secretion of anti-inflammatory molecules and to inhibit the maturation of dendritic cells. However, the effects of PSLs on osteoclasts, which are also differentiated from the common myeloid precursors, remain to be determined. This study investigated the effects of PSLs on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-β1 and PGE2, which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-κB ligand, receptor activator of NF-κB, ICAM-1, and CD44. Consistent with these in vitro observations, i.m. injection of PSLs significantly increased the plasma level of TGF-β1 and PGE2 and decreased the expression of receptor activator for NF-κB ligand, receptor activator of NF-κB, and ICAM-1 in the skeletal tissues of ankle joints of rats with adjuvant arthritis (AA). A quantitative analysis using microcomputed tomography revealed that PSLs as well as TGF-β1 together with PGE2 significantly inhibited AA-induced trabecular bone loss. These observations strongly suggest that PSLs generate TGF-β1 and PGE2 release, leading to inhibit osteoclastogenesis and AA-induced trabecular bone loss. Because PS is a component of the cell membrane, PSLs therefore can be a potentially effective pharmacological intervention against abnormal bone loss, such as osteoporosis without deleterious side effects.

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“…It was also shown that L-OA, but not H-OA, osteoblasts enhanced the formation of osteoclasts (20). A direct effect of PGE 2 on osteoclastogenesis is also possible, since Take et al (44) recently demonstrated such an effect on osteoclasts, which occurred through interactions with PGE 2 on its specific receptors.…”

Section: Discussionmentioning

confidence: 99%

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Tat¹,

Pelletier²,

Amiable³

et al. 2008

Arthritis & Rheumatism

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Objective. Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties. The purpose of this study was to investigate the importance of the ephrin system in OA subchondral bone osteoblasts.Methods. The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences of activation by ephrin B2 were determined by quantitative polymerase chain reaction. The effects of ephrin B2 activation of the EphB4 receptor on bone resorption activity were also determined. EphB4 receptor activation signaling pathways were investigated by specific enzyme-linked immunosorbent assay.Results. EphB4 receptors were present in subchondral bone osteoblasts and osteocytes. Compared with normal and H-OA osteoblasts, EphB4 receptor expression levels were significantly increased in L-OA osteoblasts, with no difference between normal and H-OA osteoblasts. EphB4 receptor levels in L-OA osteoblasts were significantly up-regulated by prostaglandin E 2 (PGE 2 ) and interleukin-17 (IL-17). Ephrin B2, PGE 2 , and IL-17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL-1␤, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-9, MMP-13, and RANKL, but not MMP-2 and osteoprotegerin. EphB4 receptor activation significantly inhibited the phosphatidylinositol 3-kinase/Akt pathway.Conclusion. This study is the first to provide evidence that EphB4 receptor activation by ephrin B2 in OA subchondral bone could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities. Ephrin B2 could be targeted as a specific therapeutic approach in the development of a diseasemodifying OA drug.Subchondral bone is made up of a specialized connective tissue formed by a mineralized matrix containing the specific type I collagen, proteoglycans, and several growth factors and cytokines, as well as bonespecific cell types (osteoblasts, osteocytes, and osteoclasts) (1,2). Osteoblast and osteoclast activities, either alone or in combination, contribute to the bone remodeling process, and any disturbance in the activities of these 2 cells is responsible for the development of altered bone metabolism.The ephrin B molecules (ephrin B1, ephrin B2, and ephrin B3) bind in a specific manner to their EphB

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Prostaglandin E2 Strongly Inhibits Human Osteoclast Formation

Cited by 79 publications

References 36 publications

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

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