scholarly journals Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lidia Ibáñez ◽  
María Luisa Ferrándiz ◽  
Rita Brines ◽  
David Guede ◽  
Antonio Cuadrado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Bone Metabolism ◽  
Bone Microarchitecture ◽  
Related Factor ◽  
Mineral Density ◽  
Trabecular Bone Mineral Density ◽  
Bone Marrow Derived Cells

Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis.Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2−/−). Bone microarchitecture was analyzed byμCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123.Results. Sham-operated or ovariectomized Nrf2−/−mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2−/−mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro.Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.

In Vivo Bioimaging Using Transgenic Rats and The Role Of Bone Marrow Cells In Wound Healing

2005 ◽  
Vol 09 (14) ◽  
pp. 652-655
Author(s):  
Takashi Murakami ◽  
Hirokazu Inoue ◽  
Eiji Kobayashi
Keyword(s):  
Bone Marrow ◽  
Wound Healing ◽  
Regenerative Medicine ◽  
Bone Marrow Cells ◽  
Transgenic Rats ◽  
Medicine Research ◽  
Bone Marrow Derived Cells ◽  
Marrow Cells

The article discusses the importance of rats in regenerative medicine research. It touches on wound healing using bone marrow derived cells and the artifical dermis.

scholarly journals Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Pan ◽  
Lin Zheng ◽  
Jiawei Fang ◽  
Ye Lin ◽  
Hehuan Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Signaling Pathways ◽  
Bone Microarchitecture ◽  
Reactive Oxygen ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species

Osteoporosis is characterized by a decrease in bone mass and destruction of the bone microarchitecture, and it commonly occurs in postmenopausal women and the elderly. Overactivation of osteoclasts caused by the inflammatory response or oxidative stress leads to osteoporosis. An increasing number of studies have suggested that intracellular reactive oxygen species (ROS) are strongly associated with osteoclastogenesis. As a novel angiotensin (Ang) II receptor blocker (ARB), azilsartan was reported to be associated with the inhibition of intracellular oxidative stress processes. However, the relationship between azilsartan and osteoclastogenesis is still unknown. In this study, we explored the effect of azilsartan on ovariectomy-induced osteoporosis in mice. Azilsartan significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and downregulated the expression of osteoclast-associated markers (Nfatc1, c-Fos, and Ctsk) in vitro. Furthermore, azilsartan reduced RANKL-induced ROS production by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistically, azilsartan inhibited the activation of MAPK/NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of azilsartan on MAPK/NF-κB signaling pathways. Consistent with the in vitro data, azilsartan administration ameliorated ovariectomy (OVX)-induced osteoporosis, and decreased ROS levels in vivo. In conclusion, azilsartan inhibited oxidative stress and may be a novel treatment strategy for osteoporosis caused by osteoclast overactivation.

scholarly journals Ablation of a small subpopulation of diabetes-specific bone marrow-derived cells in mice protects against diabetic neuropathy

2016 ◽  
Vol 310 (4) ◽  
pp. E269-E275 ◽  
Author(s):  
Hiroshi Urabe ◽  
Tomoya Terashima ◽  
Hideto Kojima ◽  
Lawrence Chan
Keyword(s):  
Bone Marrow ◽  
Diabetic Complication ◽  
Dorsal Root Ganglion Neurons ◽  
Treatment And Prevention ◽  
Bone Marrow Derived Cells ◽  
Nerve Dysfunction ◽  
Ganglion Neurons ◽  
Small Subpopulation

Diabetic peripheral neuropathy (DPN) is a major diabetic complication. Previously, we showed that hyperglycemia induces the appearance of proinsulin (PI)-producing bone marrow-derived cells (PI-BMDCs), which fuse with dorsal root ganglion neurons, causing apoptosis, nerve dysfunction, and DPN. In this study, we have devised a strategy to ablate PI-BMDCs in mice in vivo. The use of this strategy to selectively ablate TNFα-producing PI-BMDCs in diabetic mice protected these animals from developing DPN. The findings provide powerful validation for a pathogenic role of PI-BMDCs and identify PI-BMDCs as an accessible therapeutic target for the treatment and prevention of DPN.

scholarly journals The Novel Role of PGC1α in Bone Metabolism

2021 ◽  
Vol 22 (9) ◽  
pp. 4670
Author(s):  
Cinzia Buccoliero ◽  
Manuela Dicarlo ◽  
Patrizia Pignataro ◽  
Francesco Gaccione ◽  
Silvia Colucci ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Osteoblastic Differentiation ◽  
In Vivo Studies ◽  
Peroxisome Proliferator ◽  
Sirtuin 3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. Furthermore, in a mouse model of bone disease, PGC1α activation stimulates osteoblastic gene expression and inhibits atrogene transcription. PGC1α overexpression positively affects the activity of Sirtuin 3, a mitochondrial nicotinammide adenina dinucleotide (NAD)-dependent deacetylase, on osteoblastic differentiation. In vitro, PGC1α overexpression prevents the reduction of mitochondrial density, membrane potential and alkaline phosphatase activity caused by Sirtuin 3 knockdown in osteoblasts. Moreover, PGC1α influences the commitment of skeletal stem cells towards an osteogenic lineage, while negatively affects marrow adipose tissue accumulation. In this review, we will focus on recent findings about PGC1α action on bone metabolism, in vivo and in vitro, and in pathologies that cause bone loss, such as osteoporosis and type 2 diabetes.

scholarly journals Exploring the anti-apoptotic role of HAX-1 versus BCL-XL in cytokine-dependent bone marrow-derived cells from mice

FEBS Letters ◽  
2014 ◽  
Vol 588 (17) ◽  
pp. 2921-2927 ◽  
Author(s):  
Alicja Trebinska ◽  
Kari Högstrand ◽  
Alf Grandien ◽  
Ewa A. Grzybowska ◽  
Bengt Fadeel
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Derived Cells

scholarly journals A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junko Okano ◽  
Yuki Nakae ◽  
Takahiko Nakagawa ◽  
Miwako Katagi ◽  
Tomoya Terashima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Underlying Mechanism ◽  
Basal Cells ◽  
Barrier Dysfunction ◽  
Skin Injury ◽  
Accelerated Proliferation ◽  
Radiation Induced ◽  
Bone Marrow Derived Cells ◽  
Injury Recovery

AbstractExposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

2021 ◽  
pp. 1-11
Author(s):  
Hanqing Chen ◽  
Xiru Xu ◽  
Zhengqing Liu ◽  
Yong Wu
Keyword(s):  
Oxidative Stress ◽  
Vascular Remodeling ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Phenotype Switch ◽  
And Oxidative Stress

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.

Abstract 11664: The Identification and Hierarchy of Bone Marrow-Derived Artery-Resident Mesodermal Progenitor Cells and Their Dynamics in Atherosclerosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hyun-Jai Cho ◽  
Hyun-Ju Cho ◽  
Yoo-Wook Kwon ◽  
Young-Bae Park ◽  
Hyo-Soo Kim
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Circulation ◽  
Humoral Factors ◽  
Cell Property ◽  
Apoe Ko Mice ◽  
Multiplex Cytokine ◽  
Developmental Hierarchy

Background: We recently identified bone marrow (BM)-derived artery resident calcifying progenitor cells. Sca-1+PDGFRα- cells may possess bipotent (osteoblastic/osteoclastic) characteristics. However, the nature of progenitor cells remains elusive. Hypothesis: We investigated developmental hierarchy of progenitor cells and in vivo dynamics in atherosclerosis. Methods and Results: We harvested cells from BM and artery of C57 mice. In BM, Lin-CD29+Sca-1+PDGFRα- cells showed hematopoietic potential and differentiated into osteoclasts (OC). They also possessed mesenchymal stem cell property including osteoblastic (OB) differentiation, suggesting that Sca-1+PDGFRα- cells could be mesodermal progenitor cells. Interestingly, BM-derived artery-resident, clonal Sca-1+PDGFRα- cells maintained bipotency but lost hematopoietic nature. In contrast, Sca-1+PDGFRα+ cells in BM and artery only showed unipotency (OB). When we overexpressed or knocked down PDGFRα, there was no alteration in OB or OC differentiation of Sca-1+PDGFRα- cells and no effect on OB differentiation of Sca-1+PDGFRα+ cells, indicating PDGFRα as a surface marker but not a functional player. In hyperlipidemic ApoE-KO mice compared with control, Sca-1+PDGFRα- cells were less mobilized from BM to peripheral circulation and less infiltrated into atherosclerotic plaque, whereas Sca-1+PDGFRα+ cells were not significantly affected. Multiplex cytokine assay of serum and artery revealed that IL-1β was significantly increased and IL-5 was markedly decreased in atherosclerotic mice. IL-1β decreased the migration of Sca-1+PDGFRα- cells by 5 folds compared with TNFα, and IL-5 increased the migration as much as TNFα. But the migration of Sca-1+PDGFRα+ cells was not altered. These data indicate that atherosclerosis-related humoral factors mainly regulated mesodermal progenitor cells’ dynamics. Conclusion: We demonstrate that Sca-1+PDGFRα- cell is a mesodermal progenitor cell that possesses both hematopoietic and mesenchymal potentials. In atherogenesis, the mobilization and infiltration of Sca-1+PDGFRα- progenitor cells were regulated by IL-1β and IL-5. These data provide a novel mechanism regarding the role of bipotent progenitor cells in atherosclerosis.

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