Rapamycin improves bone mass in high-turnover osteoporosis with iron accumulation through positive effects on osteogenesis and angiogenesis

Wu, Jiadong; Wang, Aifei; Wang, Xiao; Li, Guangfei; Jia, Peng; Shen, Genhai; Chen, Bin; Yuan, Ye; Zhang, Hui; Yang, Fan; Xu, Youjia

doi:10.1016/j.bone.2018.12.019

Cited by 34 publications

(31 citation statements)

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“…To effectively repair bone defects duo to tumour resection, bone biomaterials should provide appropriate media for angiogenesis and osteogenesis [29]. In vitro, M2 macrophages directly regulate osteogenic differentiation of bone marrow mesenchymal stem cells [30,31].…”

Section: Introductionmentioning

confidence: 99%

Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability

Liu

et al. 2021

J Nanobiotechnol

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Background Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. Methods Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. Results Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. Conclusion The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

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Section: Introductionmentioning

confidence: 99%

Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability

Liu

et al. 2021

J Nanobiotechnol

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“…26 Autophagy plays a key role in cell survival as well as in the regulation of cell apoptosis; numerous studies have demonstrated that promoting autophagy has protective effects against various musculoskeletal diseases such as osteoarthritis and osteoporosis. 25,27 Huang et al reported that AGEs increased the ratio of LC3B/LC3A in chondrocytes. 28 Yang et al also reported that AGEs increased LC3B, while decreased P62 in osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone attenuates advanced glycation end products‐induced apoptosis and calcification by modulating autophagy in tendon‐derived stem cells

et al. 2020

J Cellular Molecular Medi

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Diabetes mellitus (DM) is one of the prominent risk factors for pathological development and progression of tendinopathy. One feature of DM-related changes in tendinopathy is accumulation of advanced glycation end products (AGEs) in affected tendons.Pioglitazone (Pio), a peroxisome proliferator-activated receptor γ agonist, performs a protective effect against AGEs. The present study aimed to investigate the pathogenetic role of AGEs on tendon-derived stem cells (TDSCs) and to determine the effect of Pio on AGEs-induced TDSC dysfunctions. Results indicated that AGEs induced TDSC apoptosis as well as compensatory activation of autophagy. Pharmacologic activation/ inhibition of autophagy leaded to alleviate/exacerbate apoptosis induced by AGEs. We further confirmed the effect of Pio on autophagy, which ameliorated apoptosis and abnormal calcification caused by AGEs both in vitro and in vivo. Thus, we suggest that Pio ameliorates the dysfunctions of TDSCs against AGEs by promoting autophagy, and we also reveal that Pio is a potential pharmacological choice for tendinopathy. K E Y W O R D Sadvanced glycation end products, apoptosis, autophagy, pioglitazone, tendon-derived stem cells

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“…This will ultimately lead to a reduced osteoporosis in the Atg7‐deleted mice, weakening the reliability of the Atg7‐deleted mice for use as a negative control for hematopoietic‐specific rescue effect in the osteoporotic model mice. Nevertheless, our recent work shows that activation of autophagy by injection of rapamycin recovered angiogenesis and osteogenesis in the induced osteoporosis mouse model, which was generated by injection of ferric ammonium citrate for iron overload (Wu et al, ). This finding generally supports our present contention that loss of autophagy in hematopoietic system compromises angiogenesis and osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

Deterioration of hematopoietic autophagy is linked to osteoporosis

et al. 2020

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Hematopoietic disorders are known to increase the risk of complications such as osteoporosis. However, a direct link between hematopoietic cellular disorders and osteoporosis has been elusive. Here, we demonstrate that the deterioration of hematopoietic autophagy is coupled with osteoporosis in humans. With a conditional mouse model in which autophagy in the hematopoietic system is disrupted by deletion of the Atg7 gene, we show that incapacitating hematopoietic autophagy causes bone loss and perturbs osteocyte homeostasis. Induction of osteoporosis, either by ovariectomy, which blocks estrogen secretion, or by injection of ferric ammonium citrate to induce iron overload, causes dysfunction in the hematopoietic stem and progenitor cells (HSPCs) similar to that found in autophagy-defective mice.Transcriptomic analysis of HSPCs suggests promotion of iron activity and inhibition of osteocyte differentiation and calcium metabolism by hematopoietic autophagy defect, while proteomic profiling of bone tissue proteins indicates disturbance of the extracellular matrix pathway that includes collagen family members. Finally, screening for expression of selected genes and an immunohistological assay identifies severe impairments in H vessels in the bone tissue, which results in disconnection of osteocytes from hematopoietic cells in the autophagy-defective mice. We therefore propose that hematopoietic autophagy is required for the integrity of H vessels that bridge blood and bone cells and that its deterioration leads to osteoporosis. SPSS 25.0. Experimental data were presented as means ± standard deviations (SDs), which was evaluated using Student's t tests.University, for their help in preparing human bone samples and creating mouse osteoporotic model, and Jin Qi from the Shanghai

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Rapamycin improves bone mass in high-turnover osteoporosis with iron accumulation through positive effects on osteogenesis and angiogenesis

Cited by 34 publications

References 50 publications

Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability

Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability

Pioglitazone attenuates advanced glycation end products‐induced apoptosis and calcification by modulating autophagy in tendon‐derived stem cells

Deterioration of hematopoietic autophagy is linked to osteoporosis

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