Tramadol enhances PGF2α-stimulated osteoprotegerin synthesis in osteoblasts

Kim, Woo; Tanabe, Kumiko; Kuroyanagi, Gen; Matsushima‐Nishiwaki, Rie; Fujita, Kazuo; Kawabata, Tetsu; Sakai, Go; Tachi, Junko; Hioki, Tomoyuki; Nakashima, Daiki; Yamaguchi, Shinobu; Otsuka, Takanobu; Tokuda, Harukuni; Kozawa, Osamu; Iida, Hiroki

doi:10.1016/j.heliyon.2020.e04779

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…Several studies have shown that PGF2α can activate the MAPK signaling pathway after coupling with the FPR [ 24 , 25 ]. MAPK signaling regulates various biological activities, among which ERK activation is crucial during the early stage of adipogenesis and is essential for PPARγ transcription [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves’ Ophthalmopathy

Zhu

Wang

et al. 2023

IJMS

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Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves’ ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves’ Ophthalmopathy

Zhu

Wang

et al. 2023

IJMS

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“…tivities in osteoblast-like MC3T3-E1 cells (Kim et al 2020). Thus, the effects of analgesic agents on the osteoprotegerin synthesis in osteoblasts might be quite different in each other.…”

Section: Effects Of Sp600125 On the Expression Levels Of Osteoprotege...mentioning

confidence: 99%

Acetaminophen reduces osteoprotegerin synthesis stimulated by PGE<sub>2</sub> and PGF<sub>2α</sub> in osteoblasts: attenuation of SAPK/JNK but not p38 MAPK or p44/p42 MAPK

et al. 2021

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Acetaminophen is one of the most widely used analgesic and antipyretic medicines, whose long-period use has reportedly been associated with an increased risk of bone fracture. However, the mechanism underlying this undesired effect remains to be investigated. The homeostatic control of bone tissue depends on the interaction between osteoblasts and osteoclasts. Osteoprotegerin produced by osteoblasts is known to play an essential role in suppressing osteoclast induction. We have previously reported that prostaglandin (PG) E 2 and PGF 2α induce osteoprotegerin synthesis through p38 mitogen-activated protein kinase (MAPK), p44/p42 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of acetaminophen on the osteoprotegerin synthesis induced by PGE 2 and PGF 2α in MC3T3-E1 cells. Acetaminophen significantly suppressed the osteoprotegerin release stimulated by PGE 2 and PGF 2α . The PGE 2 -induced expression of osteoprotegerin mRNA was also reduced by acetaminophen. Acetaminophen markedly downregulated the phosphorylation of SAPK/JNK stimulated by PGE 2 and PGF 2α , but not those of p38 MAPK or p44/p42 MAPK. SP600125, an inhibitor of SAPK/JNK, suppressed the levels of PGE 2 -and PGF 2α -upregulated osteoprotegerin mRNA expression. Taken together, these results strongly suggest that acetaminophen reduces the PGE 2 -and PGF 2α -stimulated synthesis of osteoprotegerin in osteoblasts, and that the suppressive effect is exerted via attenuation of SAPK/JNK. These findings provide a molecular basis for the possible effect of acetaminophen on bone tissue metabolism.

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Honeycomb Bionic Graphene Oxide Quantum Dot/Layered Double Hydroxide Composite Nanocoating Promotes Osteoporotic Bone Regeneration via Activating Mitophagy

Li,

Dai,

Wang

et al. 2024

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Abnormal osteogenic and remodeling microenvironment due to osteoblast apoptosis are the primary causes of delayed fracture healing in osteoporotic patients. Magnesium (Mg) alloys exhibit biodegradability and appropriate elastic moduli for bone defects in osteoporosis, but the effect on the local bone remodeling disorder is still insufficient. Inspired by the “honeycomb,” layered double hydroxide (LDH) with regular traps with graphene oxide quantum dots (GOQDs) inlayed is constructed by pulsed electrodeposition to generate GOQD/LDH composite nanocoatings on the surfaces of Mg alloy substrates. The honeycomb bionic multi‐layer stereoscopic structure shows good regulation of the degradation of Mg alloy for the support of healing time required for osteoporotic bone defect. Within its lattice, the local microenvironment conducive to osteogenesis is provided by both the rescue effect of GOQD and LDH. The osteoblast apoptosis is rescued due to the activation of mitophagy to clear dysfunctional mitochondria, where the upregulation of BNIP3 phosphorylation played a key role. The osteoporotic rat model of femoral defects confirmed the improvement of bone regeneration and osseointegration of GOQD/LDH coating. In summary, honeycomb bionic composite nanocoatings with controllable degradation and excellent pro‐osteogenic performance demonstrated a promising design strategy on Mg alloy implants in the therapy of osteoporotic bone defects.

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Tramadol enhances PGF2α-stimulated osteoprotegerin synthesis in osteoblasts

Cited by 7 publications

References 31 publications

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves’ Ophthalmopathy

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves’ Ophthalmopathy

Acetaminophen reduces osteoprotegerin synthesis stimulated by PGE<sub>2</sub> and PGF<sub>2α</sub> in osteoblasts: attenuation of SAPK/JNK but not p38 MAPK or p44/p42 MAPK

Honeycomb Bionic Graphene Oxide Quantum Dot/Layered Double Hydroxide Composite Nanocoating Promotes Osteoporotic Bone Regeneration via Activating Mitophagy

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