Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity

Meng, Jinghui; Zhang, Wenkan; Wang, Cong; Zhang, Wei; Zhou, Chenhe; Jiang, Guangyao; Hong, Jianqiao; Yan, Shigui; Yan, Wei

doi:10.1016/j.bcp.2019.113715

Cited by 51 publications

(41 citation statements)

References 45 publications

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“…37 Overexpression of PTEN inhibits RANKL-induced osteoclast formation by its negative regulation of RANKLinduced AKT and NF-κB signaling. 38 In a previous study, upregulated PTEN inhibited RANKL-induced PI3K/AKT activation. This reduced the mRNA and protein expression level of NFATc1, which correspondingly suppressed the expression of its downstream genes, including TRAP and CTSK.…”

Section: Discussionmentioning

confidence: 89%

“…This reduced the mRNA and protein expression level of NFATc1, which correspondingly suppressed the expression of its downstream genes, including TRAP and CTSK. 38 In addition to AKT/NF-κB/NFATc1 axis, AKT/GSK3β/NFATc1 signaling cascade also plays a critical role in osteoclastogenesis. 39,40 Similar to our findings, a previous study found that miR-214 can function through PI3K/Akt/NF-kB/NFATc1 pathway by PTEN.…”

Section: Discussionmentioning

confidence: 99%

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<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Zhao¹,

Liu²,

Xie³

et al. 2020

OTT

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Osteoclastogenesis is a key process in osteolytic bone metastasis (BM). Previous studies indicated that some miRNAs could regulate cancers progression and osteoclastogenesis. Our purpose was to investigate the roles of lung cancer cells-derived circulating miR-21 on osteoclastogenesis and its clinical significance in BM patients. Materials and Methods: The difference of miRNA expression in two lung cancer cell lines SBC-5 (with characteristic BM ability) and SBC-3 (without BM ability) were analyzed by microarray and qRT-PCR. Circulating miR-21 levels of lung cancer patients with or without BM were compared by qRT-PCR. The TRAP staining was used to investigate the effects of conditioned media from lung cancer cell lines or patients' plasma with different miR-21 levels on osteoclastogenesis. ROC curve was used to evaluate the diagnostic performance of circulating miR-21 in BM patients. Results: We found that miR-21 expression was specifically higher in SBC-5 than that in SBC-3 cells. The supernatants of SBC-5 cells with higher-level miR-21 promoted osteoclastogenesis. Moreover, we demonstrated that the circulating miR-21 level was significantly higher in BM patients than that in non-BM patients. The plasma from BM patients with higher-level miR-21 could also promote osteoclastogenesis. Mechanistically, lung cancer cells-derived circulating miR-21 could be transferred into osteoclast precursor cells and promote osteoclastogenesis probably by inhibiting PTEN. Finally, clinical data showed that circulating miR-21 had a potential for the diagnosis of BM. Conclusion: Overall, our findings suggested that circulating miR-21 played important roles in osteoclastogenesis of lung cancer patients and may serve as a biomarker to diagnose BM of lung cancer.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Zhao¹,

Liu²,

Xie³

et al. 2020

OTT

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“…33,34 Previous studies have demonstrated that PTEN regulates the RANKL-induced NF-κB signalling pathway during osteoclastogenesis. 35 Our findings suggested that compound 17 had a suppressive effect on RANKL-and LPSinduced osteoclastogenesis by regulating the NF-κB signalling pathway. Therefore, we investigated whether compound 17 regulated PTEN activity during RANKL-induced osteoclastogenesis.…”

Section: Compound 17 Inhibited Osteoclastogenesis By Regulating Pten mentioning

confidence: 59%

“…PTEN is a multifunctional molecule that is expressed in various types of cells and regulates multiple cellular processes, such as cell proliferation, survival, adhesion, motility and apoptosis. 35,36 The major function of PTEN is to negatively regulate several signalling pathways, such as the NF-κB pathway. 54 In recent studies, PTEN was identified as an important regulatory factor in RANKL-induced osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…54 In recent studies, PTEN was identified as an important regulatory factor in RANKL-induced osteoclastogenesis. 35 The overexpression of PTEN inhibits RANKL-induced OC formation by negatively regulating RANKL-induced NF-κB signalling. 35 In our study, we observed that compound 17 could promote the expression of total PTEN in BMMs during osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

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A selected small molecule prevents inflammatory osteolysis through restraining osteoclastogenesis by modulating PTEN activity

Chen

et al. 2020

Clinical & Translational Med

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A selected compound 17 small molecule suppressed osteoclastogenesis in vitro by inducing PTEN activity by restraining PTEN ubiquitination, thus inhibiting the RANKL-induced NF-κB pathway. The polarization and repolarization of M1 macrophages were also negatively modulated. In vivo experiments showed that compound 17 prevented LPS-induced inflammatory osteolysis by inhibiting OC activity. All in all, compound 17 might act as a potential novel drug to treat inflammatory osteolysis-related diseases in the future.

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Prussian Blue Nanozyme Normalizes Microenvironment to Delay Osteoporosis

Zhang

Zhao

et al. 2022

Adv Healthcare Materials

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Osteoporosis (OP) is the most common orthopedic disease in the elderly and the main cause of age‐related mortality and disability. However, no satisfactory intervention is currently available in clinical practice. Thus, an effective therapy to prevent or delay the development of OP should be devised. Osteoclastogenesis overactivation and excessive bone resorption are the main characteristics of OP. Accordingly, a paradigm for nanozyme‐mediated normalization of the disease microenvironment to regulate osteoclast differentiation and delay OP is proposed. Hollow Prussian blue nanozymes (HPBZs) are prepared via template‐free hydrothermal synthesis and selected as representative nanozymes. The intrinsic osteoclast activity‐remodeling bioactivities of the HPBZs are explored in vitro and in vivo, focusing on their impact on osteogenesis and specific molecular mechanisms using an OP murine model. The HPBZs significantly normalize the OP microenvironment, thereby inhibiting osteoclast formation and osteoclast resorption, possibly owing to the suppression of intracellular reactive oxygen species generation, the mitogen‐activated protein kinase, and nuclear factor κB signaling pathways. Consistently, in an ovariectomy‐induced OP murine model, HPBZ treatment significantly attenuates osteoporotic bone loss in vivo. The findings confirm the HPBZ‐mediated normalization of the disease microenvironment for the treatment of OP and suggest its application to other inflammation‐related diseases.

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Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity

Cited by 51 publications

References 45 publications

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

A selected small molecule prevents inflammatory osteolysis through restraining osteoclastogenesis by modulating PTEN activity

Prussian Blue Nanozyme Normalizes Microenvironment to Delay Osteoporosis

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