The role of EGFR signaling in age‐related osteoporosis in mouse cortical bone

Liu, Guanqiao; Xie, Yongheng; Su, Jianwen; Qin, Hanjun; Wu, Hangtian; Li, Kaiqun; Yu, Bin; Zhang, Xianrong

doi:10.1096/fj.201900436rr

Cited by 19 publications

(25 citation statements)

References 36 publications

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“…This hypothesis is further strengthened by the short time from the diagnosis of BM to the appearance of SRE (3.63 months) observed in our series and the greater distribution of these events in the first 12 months, a period in which the tumor is generally responsive to TKIs. Preclinical in vivo studies demonstrated that EGFR is essential for osteoblast proliferation (23) and down-regulated EGFR signaling was shown to favor the senescence of osteoprogenitors and the decline in bone formation on the endosteal surface of cortical bone (24). The administration of EGFR inhibitors, therefore, could impair the osteoblast mediated bone repair thus favoring the early occurrence of SREs despite the efficacy of these drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical in vivo studies demonstrated that EGFR is essential for osteoblast proliferation ( 23 ) and down-regulated EGFR signaling was shown to favor the senescence of osteoprogenitors and the decline in bone formation on the endosteal surface of cortical bone ( 24 ). The administration of EGFR inhibitors, therefore, could impair the osteoblast mediated bone repair thus favoring the early occurrence of SREs despite the efficacy of these drugs.…”

Section: Discussionmentioning

confidence: 99%

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High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases

et al. 2020

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Objectives The prevalence of Skeletal Related Adverse Events (SREs) in EGFR mutated non-small cell lung cancer (NSCLC) patients with bone metastases, treated with modern tyrosine kinase inhibitors (TKIs), has been scarcely investigated. Materials and Methods We retrospectively evaluated the data of EGFR mutated NSCLC patients with bone metastases treated with TKIs in 12 Italian centers from 2014 to 2019, with the primary aim to explore type and frequency of SREs. Results Seventy-seven out of 274 patients enrolled (28%) developed at least one major SRE: 55/274 (20%) bone fractures, 30/274 (11%) spinal cord compression, 5/274 (2%) hypercalcemia. Median time to the onset of SRE was 3.63 months. Nine patients (3%) underwent bone surgery and 150 (55%) radiation therapy on bone. SREs were more frequently observed within the 12 months from TKI start than afterwards (71 vs 29%, p 0.000). Patient Performance Status and liver metastases where independently associated with the risk of developing SREs. Median TKI exposure and overall survival were 11 and 28 months, respectively. Bone resorption inhibitors were associated with a lower risk of death (HR 0.722, 95% CI: 0.504–1.033, p = 0.075) although not statistically significant at multivariate analysis. Conclusion Bone metastatic NSCLC patients with EGFR mutated disease, treated with EGFR TKIs, have a relatively long survival expectancy and are at high risk to develop SREs. The early SRE occurrence after the TKI start provides the rationale to administer bone resorption inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases

et al. 2020

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“…EGFR signalling is critical for the survival, proliferation as well as differentiation osteoblastic cells (Liu et al, 2019; Zhang et al, 2011). Here our work shows a new role of EGFR signalling that it can mediate the internalisation of S. aureus by osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have demonstrated the over activation of epidermal growth factor receptor (EGFR) signalling in S. aureus ‐infected bone (Chen, Yao, et al, 2018; Mendoza Bertelli et al, 2016). Epidermal growth factor receptor (EGFR) is a key molecule regulating cell survival (Liu et al, 2019; Zhang et al, 2011). Crosstalk among EGFR, Src and FAK has been attributed to various cellular behaviours (Chen, Oh, et al, 2018; Pentassuglia & Sawyer, 2013).…”

Section: Introductionmentioning

confidence: 99%

EGFR / FAK and c‐Src signalling pathways mediate the internalisation of Staphylococcus aureus by osteoblasts

Hou

et al. 2020

Cellular Microbiology

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Internalisation of Staphylococcus aureus in osteoblasts plays a critical role in the persistence and recurrence of osteomyelitis, the mechanisms involved in this process remain largely unknown. In the present study, evidence of internalised S. aureus in osteoblasts was found in long bone of haematogenous osteomyelitis in mice after 2 weeks of infection. Meanwhile, eliminating extracellular S. aureus by gentamicin can partially rescue bone loss, whereas the remaining intracellular S. aureus in osteoblasts may be associated with continuous bone destruction. In osteoblastic MC3T3 cells, intracellular S. aureus was detectable as early as 15 min after infection, and the internalisation rates increased with the extension of infection time. Additionally, S. aureus invasion stimulated the expression of phosphor‐focal adhesion kinase (FAK), phosphor‐epidermal growth factor receptor (EGFR) and phosphor‐c‐Src in a time‐dependent way, and blocking EGFR/FAK or c‐Src signalling significantly reduced the internalisation rate of S. aureus in osteoblasts. Our findings provide new insights into the mechanism of S. aureus internalisation in osteoblast and raise the potential of targeting EGFR/FAK and c‐Src as adjunctive therapeutics for treating chronic S. aureus osteomyelitis.

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“…Sesamin bound to the active pocket of vascular endothelial growth factor A (VEGFA). e920485-12 which the expression of p-EGFR on the endosteal surface of cortical bone was decreased in 15-month-old mice compared with that in 3-month-old mice [51]. This finding indicated that EGFR had a relationship with age in bone metabolism.…”

Section: E920485-11mentioning

confidence: 86%

A Network Pharmacology Approach to Estimate the Active Ingredients and Potential Targets of Cuscutae semen in the Treatment of Osteoporosis

2020

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Background: Osteoporosis is a metabolic osteopathy characterized by abnormal bone mass and microstructure that has become a public health problem worldwide. Cuscutae semen (CS) is a traditional Chinese medicine (TCM) that has a positive effect on the prevention and treatment of osteoporosis. However, the mechanism of CS is unclear. Therefore, this study aimed to reveal the possible molecular mechanism involved in the effects of CS on osteoporosis based on a network pharmacology approach. Material/Methods: The inactive and active ingredients of CS were identified by searching the pharmacology analysis platform of the Chinese medicine system (TCMSP), and the targets of osteoporosis were screened in the relevant databases, such as GeneCards, PubMed, and the Comparative Toxicogenomics Database (CTD). The network of "medicine-ingredients-disease-targets (M-I-D-T)" was established by means of network pharmacology, and the key targets and core pathways were determined by R analysis. Molecular docking methods were used to evaluate the binding activity between the target and the active ingredients of CS. Results: Eleven active ingredients were identified in CS, and 175 potential targets of the active ingredients were also identified from the TCMSP. Moreover, we revealed 22 539 targets related to osteoporosis in the 3 well-established databases, and we determined the intersection of the disease targets and the potential targets of the active ingredients; 107 common targets were identified and used in further analysis. Additionally, biological processes and signaling pathways involved in target action, such as fluid shear stress, atherosclerosis, cancer pathways, and the TNF signaling pathway, were determined. Finally, we chose the top 5 common targets, CCND1, EGFR, IL6, MAPK8, and VEGFA, for molecular docking with the 11 active ingredients of CS. Conclusions: This study suggested that CS has multiple ingredients and multiple targets relevant to the treatment of osteoporosis. We determined that the active ingredient, sesamin, may be the most crucial ingredient of CS for the treatment of osteoporosis. Additionally, the network pharmacology method provided a novel research approach to analyze the function of complex ingredients.

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The role of EGFR signaling in age‐related osteoporosis in mouse cortical bone

Cited by 19 publications

References 36 publications

High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases

High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases

EGFR / FAK and c‐Src signalling pathways mediate the internalisation of Staphylococcus aureus by osteoblasts

A Network Pharmacology Approach to Estimate the Active Ingredients and Potential Targets of Cuscutae semen in the Treatment of Osteoporosis

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