HO-1: A new potential therapeutic target to combat osteoporosis

Che, Jingmin; Yang, Juhua; Zhao, Bin; Shang, Peng

doi:10.1016/j.ejphar.2021.174219

Cited by 19 publications

(16 citation statements)

References 108 publications

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“…Withdrawal estrogen increased CCR2, CCL7, and CCL2 expression but reduced PMOP in mice after inhibition of CCL7 and CCL2 synthesis by administration of band [ 39 ]. Hmox1 (HO-1) has been identified as a new potential therapeutic target against OP [ 40 , 41 ]. TBX21 gene is a T-box expressed in T cells.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] The Hub Genes Related to Osteoporosis Were Identified by Bioinformatics Analysis

Ding

Chao

et al. 2023

BioMed Research International

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Osteoporosis (OP) is commonly encountered, which is a kind of systemic injury of bone mass and microstructure, leading to brittle fractures. With the aging of the population, this disease will pose a more serious impact on medical, social, and economic aspects, especially postmenopausal osteoporosis (PMOP). This study is aimed at figuring out potential therapeutic targets and new biomarkers in OP via bioinformatics tools. After differentially expressed gene (DEG) analysis, we successfully identified 97 upregulated and 172 downregulated DEGs. They are mainly concentrated in actin binding, regulation of cytokine production, muscle cell promotion, chemokine signaling pathway, and cytokine-cytokine receiver interaction. According to the diagram of protein-protein interaction (PPI), we obtained 10 hub genes: CCL5, CXCL10, EGFR, HMOX1, IL12B, CCL7, TBX21, XCL1, PGR, and ITGA1. Expression analysis showed that Egfr, Hmox1, and Pgr were significantly upregulated in estrogen-treated osteoporotic patients, while Ccl5, Cxcl10, Il12b, Ccl7, Tbx21, Xcl1, and Itga1 were significantly downregulated. In addition, the analysis results of Pearson’s correlation revealed that CCL7 has a strong positive association with IL12b, TBX21, and CCL5 and so was CCL5 with IL12b. Conversely, EGFR has a strong negative association with XCL1 and CXCL10. In conclusion, this study screened 10 hub genes related to OP based on the GEO database, laying a biological foundation for further research on new biomarkers and potential therapeutic targets in OP.

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Section: Discussionmentioning

confidence: 99%

[Retracted] The Hub Genes Related to Osteoporosis Were Identified by Bioinformatics Analysis

Ding

Chao

et al. 2023

BioMed Research International

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“…Mitochondria is the center of REDOX balance in cells, and excess ferrous iron catalyzes the ROS generation through the Fenton reaction to disturb the REDOX balance. Excess ROS induces the apoptosis of osteoblasts by inhibiting various signaling pathways, such as Wnt/β-catenin signaling and FoxOs-mediated transcription ( 40 , 41 ). Following, we evaluated some markers of REDOX balance, including ROS levels, MDA content, SOD content and GSH content.…”

Section: Resultsmentioning

confidence: 99%

PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss

Che

Ren²,

Chen³

et al. 2023

Front. Endocrinol.

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PTH 1-34 (teriparatide) is approved by FDA for the treatment of postmenopausal osteoporosis. Iron overload is a major contributing factor for bone loss induced by unloading. Whether iron metabolism is involved in the regulation of PTH 1-34 on unloading-induced osteoporosis has not yet been reported. Here, we found that PTH 1-34 attenuated bone loss in unloading mice. PTH 1-34 regulated the disturbance of iron metabolism in unloading mice by activating Nrf2 and further promoting hepcidin expression in the liver. In addition, the Nrf2 inhibitor selectively blocked hepcidin expression in the liver of unloading mice, which neutralized the inhibitory effect of PTH 1-34 on bone loss and the recovery of iron metabolism in unloading mice. Finally, we found that PTH 1-34 promoted the differentiation and inhibited apoptosis of osteoblasts by regulating iron metabolism and maintaining redox balance under unloading conditions. Our results suggested that PTH 1-34 promoted bone formation by regulating iron metabolism under unloading conditions.

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“…The crucial finding is that TAP treatment over-expresses the inducible isoform of heme oxygenase (HMOX1), a well-established immunomodulator [ 65 , 66 , 67 ]; it has been proven that the induction of HMOX1 protects against the cytotoxicity caused by oxidative stress and apoptotic cell death, making HMOX1 an appealing target for the treatment of several chronic inflammatory diseases, including osteoporosis [ 68 ], cancer [ 69 ], acute kidney injury [ 70 ], retinal pigment epithelium degeneration [ 71 ] and Parkinson’s disease [ 56 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Polyphenols from Thinned Young Apples: HPLC-HRMS Profile and Evaluation of Their Anti-Oxidant and Anti-Inflammatory Activities by Proteomic Studies

et al. 2022

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The qualitative profile of thinned apple polyphenols (TAP) fraction (≈24% of polyphenols) obtained by purification through absorbent resin was fully investigated by LC-HRMS in positive and negative ion mode and using ESI source. A total of 68 polyphenols were identified belonging to six different classes: flavanols, flavonols, dihydrochalchones, flavanones, flavones and organic and phenolic acids. The antioxidant and anti-inflammatory activities were then investigated in cell models with gene reporter for NRF2 and NF-κB and by quantitative proteomic (label-free and SILAC) approaches. TAP dose-dependently activated NRF2 and in the same concentration range (10–250 µg/mL) inhibited NF-κB nuclear translocation induced by TNF-α and IL-1α as pro-inflammatory promoters. Proteomic studies elucidated the molecular pathways evoked by TAP treatment: activation of the NRF2 signaling pathway, which in turn up-regulates protective oxidoreductases and their nucleophilic substrates such as GSH and NADPH, the latter resulting from the up-regulation of the pentose phosphate pathway. The increase in the enzymatic antioxidant cellular activity together with the up-regulation of the heme-oxygenase would explain the anti-inflammatory effect of TAP. The results suggest that thinned apples can be considered as a valuable source of apple polyphenols to be used in health care products to prevent/treat oxidative and inflammatory chronic conditions.

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HO-1: A new potential therapeutic target to combat osteoporosis

Cited by 19 publications

References 108 publications

[Retracted] The Hub Genes Related to Osteoporosis Were Identified by Bioinformatics Analysis

[Retracted] The Hub Genes Related to Osteoporosis Were Identified by Bioinformatics Analysis

PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss

Polyphenols from Thinned Young Apples: HPLC-HRMS Profile and Evaluation of Their Anti-Oxidant and Anti-Inflammatory Activities by Proteomic Studies

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