Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance

Cui, Zichen; Feng, Changgong; Chen, Jiazheng; Wang, Yi; Meng, Qing-Hao; Zhao, Siming; Zhang, Yuanji; Feng, Dianjie; Li, Ziqing

doi:10.1155/2022/4913534

Cited by 7 publications

(2 citation statements)

References 55 publications

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“…The primary osteoclastogenic factor is RANKL which triggers a complex network of signaling pathways including NF-kB and mitogen-activated protein kinases (MAPK), via the receptor RANK on OC progenitors. By further activating the nuclear factor of activated T cells c1 (NFATc1), the master transcriptional factor of osteoclastogenesis, the fate of OC progenitors is decided by the controlling of key osteoclastogenic genes, such as tartrateresistant acid phosphatase (TRAP) and cathepsin K (CTSK) (113)(114)(115). Calcineurin, a powerful mediator of transcriptional activity of NFATc1, is regulated by cytosolic calcium (Ca 2+ ) downstream of the TEC kinases and phospholipase Cg (PLCg), all of which are governed by both RANK and immunoreceptor tyrosine-based activation motif (ITAM)-based signaling.…”

Section: Bone Remodeling and Osteoclastogenesismentioning

confidence: 99%

Macrophages in aseptic loosening: Characteristics, functions, and mechanisms

et al. 2023

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Aseptic loosening (AL) is the most common complication of total joint arthroplasty (TJA). Both local inflammatory response and subsequent osteolysis around the prosthesis are the fundamental causes of disease pathology. As the earliest change of cell behavior, polarizations of macrophages play an essential role in the pathogenesis of AL, including regulating inflammatory responses and related pathological bone remodeling. The direction of macrophage polarization is closely dependent on the microenvironment of the periprosthetic tissue. When the classically activated macrophages (M1) are characterized by the augmented ability to produce proinflammatory cytokines, the primary functions of alternatively activated macrophages (M2) are related to inflammatory relief and tissue repair. Yet, both M1 macrophages and M2 macrophages are involved in the occurrence and development of AL, and a comprehensive understanding of polarized behaviors and inducing factors would help in identifying specific therapies. In recent years, studies have witnessed novel discoveries regarding the role of macrophages in AL pathology, the shifts between polarized phenotype during disease progression, as well as local mediators and signaling pathways responsible for regulations in macrophages and subsequent osteoclasts (OCs). In this review, we summarize recent progress on macrophage polarization and related mechanisms during the development of AL and discuss new findings and concepts in the context of existing work.

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Section: Bone Remodeling and Osteoclastogenesismentioning

confidence: 99%

Macrophages in aseptic loosening: Characteristics, functions, and mechanisms

et al. 2023

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“…Professor Hopkins, a pharmacologist from the University of Dundee in the United Kingdom, introduced the network pharmacology approach to address the intricate nature of TCM. This method aids in the establishment of a comprehensive network connecting components, targets, diseases, and molecular pathways [15,16]. In addition, molecular docking can predict the binding affinity between ligands and receptors by simulating their interactions.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma

Wei,

Meng,

Xiang

et al. 2024

BMC Complement Med Ther

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Objective The main objectives of this study were to identify the active components of Tongguanteng injection (TGT) and investigate the preclinical efficacy and mechanism of TGT on osteosarcoma using a combination of network pharmacology and experimental validation. Methods To identify the active constituents and targets of TGT against osteosarcoma using network pharmacology, we constructed a network consisting of an 'active ingredient-disease-target-pathway' and a protein–protein interaction (PPI) network. The target organ network was utilized to investigate the distribution of core targets in tissues. Afterwards, the core targets underwent Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The binding energy between receptors and ligands was compared using molecular docking. In addition, SwissADME was employed to forecast the pharmacokinetic characteristics of the substances. Finally, real-time polymerase chain reaction (RT-PCR), cell proliferation assay, morphological analysis, apoptosis assay, mitochondrial membrane potential (MMP) detection, and Western blotting were utilized to confirm the potential mechanisms of TGT treatment in osteosarcoma cell lines 143B and SAOS2. Results A total of 54 chemical constituents of TGT and 71 targets associated with osteosarcoma were acquired. Through the molecular docking technology, Tenacigenin B, Marsdekoiside, Taraxasterol, Tenacissoside G, Tenacissoside L, and Tenacissoside J were identified as the primary active components of TGT among the various compounds. Analysis of target organs suggests that TGT may play an anti-osteosarcoma role through immune regulation. The GO and KEGG enrichment analysis revealed that TGT could trigger osteosarcoma cell apoptosis by inhibiting the HIF-1 signalling pathway and modulating PD-1 expression and the PD-1 checkpoint pathway in cancer. SwissADME database predicted that Tenacigenin B and Taraxasterol had the best drug-likeness. In vitro studies also demonstrated that TGT suppressed the activity and induced alterations in the morphology of osteosarcoma cells. It decreased MMP levels, triggered apoptosis by increasing Bax expression and Caspase-3 activity, and decreased Bcl-2 expression, thereby exerting an anti-osteosarcoma effect. In the meantime, RT-PCR tests demonstrated that TGT could control immune response against tumors and hinder the proliferation and spread of cancerous cells by impacting the levels of critical factors, including JUN, HSP90AA1, HDAC1, and CDK1. Conclusion The study accurately anticipated the active components, targets, and pathways of TGT in the management of osteosarcoma. The molecular mechanism of TGT-induced apoptosis in osteosarcoma cells was demonstrated by in vitro experiments. These results provide theoretical and technical support for TGT as a clinical adjuvant drug for osteosarcoma.

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