3,5-dicaffeoyl‑epi-quinic acid from Atriplex gmelinii enhances the osteoblast differentiation of bone marrow-derived human mesenchymal stromal cells via WnT/BMP signaling and suppresses adipocyte differentiation via AMPK activation

Karadeniz, Fatih; Oh, Jung Hwan; Lee, Jung Im; Seo, Youngwan; Kong, Chang‐Suk

doi:10.1016/j.phymed.2020.153225

Cited by 15 publications

(18 citation statements)

References 38 publications

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“…Consequently, 3T3-L1 cells treated along the differentiation time with 10 µM DCQA display less lipid droplet deposition than not-treated ones, as evidenced by Oil Red O incorporation ( Figure 2 B,C). Our data agree with a previous report of Karadeniz et al [ 47 ] in which 3T3-L1 adipogenesis, via AMPK activation, was suppressed by the administration of 3,5-dicaffeoyl-epi-quinic acid, an isomer of 3,5-DCQA used by us. Furthermore, other studies converge on the anti-adipogenesis effects of several caffeoylquinic acid compounds purified from different natural sources.…”

Section: Discussionsupporting

confidence: 94%

3,5-Dicaffeoylquinic Acid Lowers 3T3-L1 Mitotic Clonal Expansion and Adipocyte Differentiation by Enhancing Heme Oxygenase-1 Expression

Raineri

Campagnari

Toso³

et al. 2021

Molecules

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Adipogenesis is a complex process in which cell commitment and mitotic clonal expansion (MCE) are in-sequence crucial events leading to terminal adipocyte differentiation. The molecules able to block some key signals in this cascade can hamper adipogenesis becoming promising agents to counteract hyperplasia and hypertrophy of adipose tissue. Mono- and di-caffeoylquinic acid isomers are biologically active polyphenols, displaying in vitro and in vivo antioxidant, hepatoprotective, anti-diabetic and anti-obesity properties. Among these isomers, 3,5-dicaffeoylquinic acid (DCQA) has been reported to inhibit lipid accumulation in adipose cells more successfully than others. Thus, we investigated DCQA effects and molecular mechanisms on 3T3-L1 pre-adipocytes induced to differentiate with a hormonal cocktail (MDI). Oil Red O incorporation assessed that DCQA pre-treatment inhibited lipid accumulation in 3T3-L1 cells induced to differentiate for 10 days. At this time, an increased phosphorylation of both AMP-activated kinase and acetyl-CoA carboxylase, as well as a strong decrease in fatty acid synthase protein level, were registered by immunoblotting, thereby suggesting that DCQA treatment can reduce fatty acid anabolism in 3T3-L1 adipocytes. Furthermore, BrdU incorporation assay, performed 48 h after hormonal stimulation, revealed that DCQA treatment was also able to hinder the 3T3-L1 cell proliferation during the MCE, which is an essential step in the adipogenic process. Thus, we focused our attention on early signals triggered by the differentiation stimuli. In the first hours after hormonal cocktail administration, the activation of ERK1/2 and Akt kinases, or CREB and STAT3 transcription factors, was not affected by DCQA pre-treatment. Whereas 24 h after MDI induction, DCQA pre-treated cells showed increased level of the transcription factor Nrf2, that induced the expression of the antioxidant enzyme heme oxygenase 1 (HO-1). In control samples, the expression level of HO-1 was reduced 24 h after MDI induction in comparison with the higher amount of HO-1 protein found at 2 h. The HO-1 decrease was functional by allowing reactive oxygen species to boost and allowing cell proliferation induction at the beginning of MCE phase. Instead, in DCQA-treated cells the HO-1 expression was maintained at high levels for a further 24 h; in fact, its expression decreased only 48 h after MDI stimulation. The longer period in which HO-1 expression remained high led to a delay of the MCE phase, with a subsequent inhibition of both C/EBP-α expression and adipocyte terminal differentiation. In conclusion, DCQA counteracting an excessive adipose tissue expansion may become an attractive option in obesity treatment.

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Section: Discussionsupporting

confidence: 94%

3,5-Dicaffeoylquinic Acid Lowers 3T3-L1 Mitotic Clonal Expansion and Adipocyte Differentiation by Enhancing Heme Oxygenase-1 Expression

Raineri

Campagnari

Toso³

et al. 2021

Molecules

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“…Previous literature reports that high levels of Wnt signaling, an important signaling pathway that regulates osteogenic differentiation, can be activated in osteogenic differentiation of BMSCs and promote bone formation ( Wang et al, 2017 ; Zhu et al, 2019 ). In osteoporotic mice, the level of Wnt ligand protein was reduced, and the activity of the entire pathway was decreased ( Karadeniz et al, 2020 ). Therefore, the Wnt/β-catenin signaling pathway is a critical signaling pathway in osteogenic differentiation of BMSCs.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that the modification or fixation of surface coatings and biological functional molecules will facilitate osseointegration. Recently, due to the study of cell response to physical signals, the mechanical stress on the implant has attracted the attention of many researchers (Lee et al, 2020). BMSCs have a variety of differentiation potentials, and many researchers have indicated that differentiation and phenotypic expression of BMSCs can be affected by mechanical signals (Wang et al, 2016;Huang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

Liu

Cheng

Zhao

et al. 2021

Front. Bioeng. Biotechnol.

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Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

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“…Hyperoside protects osteoblasts from oxidative stress [74,75], while astragalin stimulates differentiation of osteoblasts [76]. Additionally, quinic acid promotes osteoblasts differentiation through activation of the Wnt/β-catenin pathway, while caftaric acid modulates RunX2 and RANKL/OPG signalling pathways [77].…”

Section: Discussionmentioning

confidence: 99%

Osteoprotective Effects of ‘Anti-Diabetic’ Polyherbal Mixture in Type 1 Diabetic Rats

et al. 2021

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Bone loss leading to osteopenia and osteoporosis is a frequent secondary complication of diabetes. This study aimed to evaluate the value of a traditionally used ‘anti-diabetic’ polyherbal mixture as a possible remedy for the prevention of this complication. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate. The animals with blood glucose higher than 20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, animals were treated with two concentrations of the polyherbal mixture (10 and 20 g of dry plant material/ kg). Bone histopathology was evaluated using the H&E and Masson’s trichrome staining. Alloxan-induced diabetes triggered bone histological changes characteristic for the development of osteopenia and osteoporosis and treatment with the polyherbal decoction restored these histopathological changes of the bones to the healthy animal level. At the same time, treatment with these tested doses has shown no adverse effects. These findings suggest that this mixture might be used as a remedy for the prevention of diabetic bone loss.

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3,5-dicaffeoyl‑epi-quinic acid from Atriplex gmelinii enhances the osteoblast differentiation of bone marrow-derived human mesenchymal stromal cells via WnT/BMP signaling and suppresses adipocyte differentiation via AMPK activation

Cited by 15 publications

References 38 publications

3,5-Dicaffeoylquinic Acid Lowers 3T3-L1 Mitotic Clonal Expansion and Adipocyte Differentiation by Enhancing Heme Oxygenase-1 Expression

3,5-Dicaffeoylquinic Acid Lowers 3T3-L1 Mitotic Clonal Expansion and Adipocyte Differentiation by Enhancing Heme Oxygenase-1 Expression

Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

Osteoprotective Effects of ‘Anti-Diabetic’ Polyherbal Mixture in Type 1 Diabetic Rats

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