Cross‐talk Between Histone and DNA Methylation Mediates Bone Loss in Hind Limb Unloading

Author(s):  
Bing Li ◽  
Jie Zhao ◽  
Jianxiong Ma ◽  
Weibo Chen ◽  
Ce Zhou ◽  
...  
2018 ◽  
Vol 63 (1) ◽  
pp. 42-49 ◽  
Author(s):  
Yu Matsumoto ◽  
Yuko Tousen ◽  
Yoshiko Ishimi

Bone Reports ◽  
2020 ◽  
Vol 13 ◽  
pp. 100688
Author(s):  
Laura Peurière ◽  
Carmelo Mastrandrea ◽  
Marie-Hélène Lafage-Proust ◽  
Laurence Vico

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 59-59
Author(s):  
Yuko Tousen ◽  
Takashi Kondo ◽  
Tsuyoshi Chiba ◽  
Yoshiko Ishimi

Abstract Objectives Osteoporosis is a major health problem in the elderly characterized by bone loss and micro-architectural deterioration of bone tissue and associated with an increased risk of fracture. Prolonged bed rest, or physical inactivity during space flight causes rapid and marked bone loss. The effects of catechin, the main ingredient of Japanese green tea, on the bone are currently under study. It has been shown that green tea catechin modulates bone resorption in osteoclasts. However, there is no evidence supporting its inhibitory effect on bone loss during physical inactivity. In the present study, we investigated whether green tea catechin prevented bone loss through skeletal hindlimb-unloading in mice. Methods Female 8-week-old ddY mice were divided into five groups (n = 6–8 each) and subjected to: (1) normal housing fed a control diet, (2) sham unloading fed a control diet, (3) hind limb-unloading fed a control diet, (4) hind limb-unloading fed a 0.05% epigallocatechin gallate (EGCG)-containing diet, and (5) hind limb-unloading fed a 0.25% EGCG-containing diet for three weeks. Purified EGCG (97%) was used for green tea catechin. Results Bone mineral density of the tibia significantly decreased in hind limb-unloading mice. Treatment with 0.25% EGCG prevented bone loss and maintained trabecular bone mineral density more significantly than in cortical bones. The 0.25% EGCG diet inhibited decrease in the gene expression of alkaline phosphatase, a marker of bone formation, in the bone marrow in hind limb-unloading mice. Conclusions These results suggest that EGCG has ability to prevent bone loss induced by hindlimb-unloading in mice. These osteoprotective effects of EGCG may result from the inhibition of unloading-induced decrease in bone formation. Funding Sources This work was supported by the Honjo International Scholarship Foundation of Japan.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chandrasekhar Kesavan ◽  
Nikita M. Bajwa ◽  
Heather Watt ◽  
Subburaman Mohan

AbstractGrowth hormone (GH) deficiency and loss of physical activity are common features in traumatic brain injury (TBI) patients that may contribute to bone loss. Therefore, we tested the hypothesis that GH treatment will rescue the hind limb unloading (UL)-induced skeletal deficit in TBI mice. Mild TBI was induced once per day for four consecutive days. UL (right hind limb) and treatment (3 mg/day GH or vehicle) began two weeks after the first TBI episode and lasted for four weeks. GH treatment increased femur BMD and lean body mass but decreased the % fat measured by DXA in the Control group. Micro-CT analysis revealed that the TBI, UL and TBI-UL groups showed reduced tibia trabecular (Tb) bone mass by 15%, 70%, and 75%, respectively compared to Control mice and that GH treatment significantly increased Tb. bone mass in all four groups. Vertebra also showed reduced Tb. bone mass in TBI, UL and TBI-UL groups. GH treatment increased vertebral Tb. bone mass in Control and UL groups but not in the TBI or TBI-UL group. GH treatment increased serum IGF-I levels similarly in TBI, UL and TBI-UL groups at day 14, suggesting the GH effect on liver IGF-I production was unaffected by skeletal UL. In contrast, GH effect on expression of ALP, IGFBP5 and axin2 in bone were compromised by UL. In conclusion, skeletal UL caused a greater Tb. bone deficit than mild TBI alone and that GH anabolic effects in the TBI and UL groups vary depending on the skeletal site.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 199
Author(s):  
Urara Tanaka ◽  
Shunichi Kajioka ◽  
Livia S. Finoti ◽  
Daniela B. Palioto ◽  
Denis F. Kinane ◽  
...  

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.


1999 ◽  
Vol 14 (10) ◽  
pp. 1708-1713 ◽  
Author(s):  
Timo Jämsä ◽  
Antti Koivukangas ◽  
Jorma Ryhänen ◽  
Pekka Jalovaara ◽  
Juha Tuukkanen

2009 ◽  
Vol 80 (2) ◽  
pp. 88-93 ◽  
Author(s):  
Pengfei Yang ◽  
Bin Jia ◽  
Chong Ding ◽  
Zhe Wang ◽  
Airong Qian ◽  
...  

2009 ◽  
Vol 43 (4) ◽  
pp. e-1-e-9
Author(s):  
N. Rodionova ◽  
V. Oganov

Peculiarity of Ultrastructure and45Ca Methabolism of Osteoclasts in Conditions of Hind Limb Unloading and MicrogravityUsing methods of electron microscopy, morphometry and cytochemistry the peculiarities of ultrastructure of osteoclasts and resorptive processes of the mineralized matrix in spongy bone of the rat femoral bone metaphyses following the experimental hind limb unloading model (28 days), as well as in rats exposed on American Space Station SLS—2 (2 weeks) were studied. The methods of light and electron microscopy radioautography45Ca were used in the experiment of hind limbs unloading. The results of investigations demonstrated that in zones of adaptive remodeling the resorption and destruction processes in the bone tissue increase under the supportive unloading. It takes place by increasing of functional activity of osteoclasts (in microgravity conditions we registered the «giant» osteoclasts). The dynamics of45Ca —incorporation into osteoclasts is an indicator of a direct involvement of cells in calcium transfer from the resorpting mineralized matrix to intercellular environment and intensification of this process at hind limb unloading model.


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