scholarly journals m6A Methylation Regulates Osteoblastic Differentiation and Bone Remodeling

2021 ◽  
Vol 9 ◽  
Author(s):  
Mei Huang ◽  
Shaozhe Xu ◽  
Lifei Liu ◽  
Miao Zhang ◽  
Jianmin Guo ◽  
...  
Keyword(s):  
Bone Health ◽  
Nuclear Export ◽  
Osteoporosis Treatment ◽  
Osteoblastic Differentiation ◽  
Cellular Level ◽  
Bone Homeostasis ◽  
Treatment Of Osteoporosis ◽  
New Approach ◽  
Marrow Mesenchymal Stem Cells ◽  
Adenosine Nucleotide

Osteoporosis is a prevalent bone disease of the aging population, which is characterized by a decrease in bone mass because of the imbalance of bone metabolism. Although the prevention and treatment of osteoporosis have been explored by different researchers, the mechanisms underlying osteoporosis are not clear exactly. N6 methyladenosine (m6A) is a methylated adenosine nucleotide, which functions through its interaction with the proteins called “writers,” “readers” and “erasers.” The epigenetic regulation of m6A has been demonstrated to affect mRNA processing, nuclear export, translation, and splicing. At the cellular level, m6A modification has been known to affect cell proliferation, differentiation, and apoptosis of bone-related cells, such as bone marrow mesenchymal stem cells (BMSC), osteoblasts, and osteoclasts by regulating the expression of ALP, Runx2, Osterix, VEGF, and other related genes. Furthermore, PTH/Pth1r, PI3K‐Akt, Wnt/β‐Catenin, and other signaling pathways, which play important roles in the regulation of bone homeostasis, are also regulated by m6A. Thus, m6A modification may provide a new approach for osteoporosis treatment. The key roles of m6A modification in the regulation of bone health and osteoporosis are reviewed here in this article.

scholarly journals The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Wacili Da ◽  
Lin Tao ◽  
Yue Zhu
Keyword(s):  
Energy Metabolism ◽  
Bone Resorption ◽  
Oxidative Phosphorylation ◽  
Bone Homeostasis ◽  
Treatment Of Osteoporosis ◽  
New Approach ◽  
Metabolism Disorder ◽  
Osteoclast Survival ◽  
Energy Metabolism Disorder

In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in the occurrence and development of osteoporosis. However, the mechanism underlying the osteoclast energy metabolism disorder that interferes with bone homeostasis has not been determined. Bone resorption by osteoclasts is a process that consumes large amounts of adenosine triphosphate (ATP) produced by glycolysis and oxidative phosphorylation. In addition to glucose, fatty acids and amino acids can also be used as substrates to produce energy through oxidative phosphorylation. In this review, we summarize and analyze the energy-based phenotypic changes, epigenetic regulation, and coupling with systemic energy metabolism of osteoclasts during the development and progression of osteoporosis. At the same time, we propose a hypothesis, the compensatory recovery mechanism (involving the balance between osteoclast survival and functional activation), which may provide a new approach for the treatment of osteoporosis.

scholarly journals PTHG2 Reduces Bone Loss in Ovariectomized Mice by Directing Bone Marrow Mesenchymal Stem Cell Fate

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jiao Chen ◽  
Hao Zhang ◽  
Xianmin Wu ◽  
Fuxiao Wang ◽  
Yili Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Adipogenic Differentiation ◽  
Osteoblastic Differentiation ◽  
Mice Model ◽  
Treatment Of Osteoporosis ◽  
Ovariectomized Mice ◽  
Marrow Mesenchymal Stem Cells ◽  
Hydrolysis Resistance

Teriparatide, also known as 1-34 parathyroid hormone (PTH (1-34)), is commonly used for the treatment of osteoporosis in postmenopausal women. But its therapeutic application is restricted by poor metabolic stability, low bioavailability, and rapid clearance. Herein, PTHG2, a glycosylated teriparatide derivative, is designed and synthesized to improve PTH stability and exert more potent antiosteoporosis effect. Surface plasmon resonance (SPR) analysis shows that PTHG2 combines to PTH 1 receptor. Additional acetylglucosamine covalent bonding in the first serine at the N terminal of PTH (1-34) improves stability and increases protein hydrolysis resistance. Intermittent administration of PTHG2 preserves bone quality in ovariectomy- (OVX-) induced osteoporosis mice model, along with increased osteoblastic differentiation and bone formation, and reduced marrow adipogenesis. In vitro, PTHG2 inhibits adipogenic differentiation and promotes osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs). For molecular mechanism, PTHG2 directs BMSCs fate through stimulating the cAMP-PKA signaling pathway. Blocking PKA abrogates the pro-osteogenic effect of PTHG2. In conclusion, our study reveals that PTHG2 can accelerate osteogenic differentiation of BMSCs and inhibit adipogenic differentiation of BMSCs and show a better protective effect than PTH (1-34) in the treatment of osteoporosis.

scholarly journals Protein secondary structures (α-helix and β-sheet) at a cellular level and protein fractions in relation to rumen degradation behaviours of protein: a new approach

2005 ◽  
Vol 94 (5) ◽  
pp. 655-665 ◽  
Author(s):  
Peiqiang Yu
Keyword(s):  
Nutritive Value ◽  
Secondary Structures ◽  
Cellular Level ◽  
Heat Processing ◽  
Molecular Chemistry ◽  
New Approach ◽  
Ftir Microspectroscopy ◽  
Protein Secondary Structures ◽  
Α Helix ◽  
Β Sheet

Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the α-helix and β-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of β-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution (∼10 μm). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of α-helixes and β-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P<0·05) the percentage of α-helixes (from 47·1 % to 36·1 %: S-FTIR absorption intensity), increased the percentage of β-sheets (from 37·2 % to 49·8 %: S-FTIR absorption intensity) and reduced the α-helix to β-sheet ratio (from 0·3 to 0·7) in the golden flaxseeds, which indicated a negative effect of the roasting on protein values, utilisation and bioavailability. These results were proved by the Cornell Net Carbohydrate Protein System in situ animal trial, which also revealed that roasting increased the amount of protein bound to lignin, and well as of the Maillard reaction protein (both of which are poorly used by ruminants), and increased the level of indigestible and undegradable protein in ruminants. The present results demonstrate the potential of highly spatially resolved synchrotron-based infrared microspectroscopy to locate ‘pure’ protein in feed tissues, and reveal protein secondary structures and digestive behaviour, making a significant step forward in and an important contribution to protein nutritional research. Further study is needed to determine the sensitivities of protein secondary structures to various heat-processing conditions, and to quantify the relationship between protein secondary structures and the nutrient availability and digestive behaviour of various protein sources. Information from the present study arising from the synchrotron-based IR probing of the protein secondary structures of protein sources at the cellular level will be valuable as a guide to maintaining protein quality and predicting digestive behaviours.

scholarly journals The use of PTH in the treatment of osteoporosis

2010 ◽  
Vol 54 (2) ◽  
pp. 213-219 ◽  
Author(s):  
Victória Z. Cochenski Borba ◽  
Nádila Cecyn Pietszkowski Mañas
Keyword(s):  
Parathyroid Hormone ◽  
Bone Density ◽  
Adverse Effects ◽  
Combination Therapy ◽  
Biochemical Markers ◽  
Osteoporosis Treatment ◽  
Antiresorptive Therapy ◽  
Treatment Of Osteoporosis ◽  
Antiresorptive Agents ◽  
Anabolic Treatment

Anabolic drugs have recently widened therapeutic options in osteoporosis treatment, as they influence processes associated with bone formation to a greater extent and earlier than bone reabsortion. They positively affect a number of skeletal properties besides bone density, as intermittent administration of parathyroid hormone (PTH) results in an increase in the number and activity of osteoblasts leading to an increase in bone mass and improvement in skeletal architecture at both the trabecular and cortical bone. Human recombinant parathyroid hormone (hrPTH 1-84) and human recombinant PTH peptide 1-34 (teriparatide) belong to this group. The objective of this paper is to review PTH actions, benefits and adverse effects, action on biochemical markers, combination therapy with antiresorptive agents, impact of antiresorptive therapy prior to anabolic treatment, sequential treatment, and effect on glucocorticoid-induced osteoporosis.

scholarly journals Glucocorticoid-induced osteoporosis in systemic lupus erythematosus

2018 ◽  
Vol 3 ◽  
pp. 205990211880251
Author(s):  
Kee Fong Phang ◽  
Jiacai Cho ◽  
Weixian Lee ◽  
Anselm Mak
Keyword(s):  
Bone Mineral Density ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Bone Health ◽  
Mineral Density ◽  
Systemic Lupus ◽  
Treatment Of Osteoporosis ◽  
Improvement In Survival ◽  
Prevalence Of Osteoporosis

Improvement in survival of systemic lupus erythematosus has been brought about with new advancement in treatment. However, glucocorticoids remain the sole cornerstone and as patients live longer, there is a need to address long-term complications brought by long-term glucocorticoid use such as osteoporosis. In this review, glucocorticoid-induced osteoporosis in systemic lupus erythematosus will be extensively discussed. This would include prevalence of osteoporosis in systemic lupus erythematosus patients, the difficulties in measuring fracture risk and pitfalls in using conventional methods such as bone mineral density. In addition, the mechanism of actions of glucocorticoids and evidence for glucocorticoids in the treatment of specific systemic lupus erythematosus manifestations would be explored and we also discussed specific pathophysiological mechanisms in the development of glucocorticoid-induced osteoporosis in systemic lupus erythematosus. We also reviewed the latest guidelines in the treatment of glucocorticoid-induced osteoporosis and the evidence for various osteoporosis medications. Finally, we recommend an approach in monitoring bone health and the treatment of osteoporosis specifically in systemic lupus erythematosus patients.

scholarly journals HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xueman Zhou ◽  
Wenxiu Yuan ◽  
Xin Xiong ◽  
Zhenzhen Zhang ◽  
Jiaqi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Cells ◽  
Current Knowledge ◽  
Bone Microarchitecture ◽  
Osteoporosis Treatment ◽  
Bone Fragility ◽  
Heme Oxygenase 1 ◽  
Bone Homeostasis ◽  
Mass Reduction ◽  
Bone Biology

Osteoporosis is a prevalent bone disorder characterized by bone mass reduction and deterioration of bone microarchitecture leading to bone fragility and fracture risk. In recent decades, knowledge regarding the etiological mechanisms emphasizes that inflammation, oxidative stress and senescence of bone cells contribute to the development of osteoporosis. Studies have demonstrated that heme oxygenase 1 (HO-1), an inducible enzyme catalyzing heme degradation, exhibits anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. Emerging evidence has revealed that HO-1 is critical in the maintenance of bone homeostasis, making HO-1 a potential target for osteoporosis treatment. In this Review, we aim to provide an introduction to current knowledge of HO-1 biology and its regulation, focusing specifically on its roles in bone homeostasis and osteoporosis. We also examine the potential of HO-1-based pharmacological therapeutics for osteoporosis and issues faced during clinical translation.

scholarly journals Nutritional aspects of the prevention and treatment of osteoporosis

2010 ◽  
Vol 54 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Bárbara Santarosa Emo Peters ◽  
Lígia Araújo Martini
Keyword(s):  
Bone Mass ◽  
Bone Health ◽  
Critical Role ◽  
Bone Fragility ◽  
Vitamin Supplementation ◽  
Treatment Of Osteoporosis ◽  
Age Related ◽  
Consequent Increase ◽  
Global Health Problem ◽  
Optimal Protection

Osteoporosis is a global health problem characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Nutrition plays a critical role in reducing the risk of osteoporosis through its effect on all of these fragility factors, especially on the development and maintenance of bone mass. An adequate calcium, vitamin D and protein intake resulted in reduced bone remodeling, better calcium retention, reduced age-related bone loss, and reduced fracture risk. Recent evidence indicates that a healthy dietary pattern including dairy products (mainly fat free), fruit and vegetables and adequate amounts of meat, fish and poultry is positively related to bone health. Furthermore, mineral and vitamin supplementation should be closely monitored by health professionals since it could have adverse effects and be insufficient to ensure optimal protection of bone health.

scholarly journals 08 Evidence Base for Treatment of Osteoporosis in Older People

2019 ◽  
Vol 48 (Supplement_4) ◽  
pp. iv3-iv3
Author(s):  
Tahir Masud
Keyword(s):  
Oldest Old ◽  
Age Groups ◽  
Osteoporotic Fractures ◽  
Osteoporosis Treatment ◽  
Fracture Reduction ◽  
Older Population ◽  
Term Care ◽  
Treatment Of Osteoporosis ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract After the age of fifty years the prevalence of osteoporosis and incidence of osteoporotic fractures rise substantially with age. It is ironic however that the pivotal trials for the common drugs used to treat osteoporosis mainly recruited participants under the age of 80 years leading some to question the use of these drugs in the older population. This talk explores the evidence accumulated for the treatment of osteoporosis in the frailer older population. The FOSIT trial showed a 47% reduction in non-vertebral fractures with alendronate in people up to 84 years, and a study in long term care in those up to 91 years showed a significant improvement in bone density at the spine and hip. A post hoc analysis of the risedronate HIP trial in people aged 70-100 years with established osteoporosis showed a 47% reduction in hip fractures. In the zoledronic acid Horizon studies fractures were significantly reduced in a population up to the age of 89 years and mortality was reduced by 28%, with half of the participants being older than 75 years. Interestingly a post hoc analysis showed that those participants who ended up having only a single infusion had a reduction of all clinical fractures at 3 years. The Freedom trial of denosumab was performed in a population aged up to 90 years with significant fracture reduction across all age groups. Studies with the anabolic agent teriparatide showed that vertebral and non-vertebral fracture reduction occurred in both the under and over 75 age groups. Trials with the recently developed agents abaloparatide and romosozumab have shown significant fracture reductions in populations up to ages of 86 and 90 years respectively. There is now enough evidence to suggest that the oldest old should be considered for osteoporosis treatment as well having a focus on falls reduction.

scholarly journals METTL3 Modulates Osteoclast Differentiation and Function by Controlling RNA Stability and Nuclear Export

2020 ◽  
Vol 21 (5) ◽  
pp. 1660 ◽  
Author(s):  
Di Li ◽  
Luhui Cai ◽  
Runsha Meng ◽  
Zhihui Feng ◽  
Qiong Xu
Keyword(s):  
Nuclear Export ◽  
Osteoclast Differentiation ◽  
Rna Stability ◽  
Cell Lineage ◽  
Specific Gene ◽  
Bone Homeostasis ◽  
Protein Levels ◽  
Lineage Differentiation ◽  
And Function ◽  
Skeletal Integrity

Osteoclast differentiation and function are crucial for maintaining bone homeostasis and preserving skeletal integrity. N6-methyladenosine (m6A) is an abundant mRNA modification that has recently been shown to be important in regulating cell lineage differentiation. Nevertheless, the effect of m6A on osteoclast differentiation remains unknown. In the present study, we observed that the m6A level and methyltransferase METTL3 expression increased during osteoclast differentiation. Mettl3 knockdown resulted in an increased size but a decreased bone-resorbing ability of osteoclasts. The expression of osteoclast-specific genes (Nfatc1, c-Fos, Ctsk, Acp5 and Dcstamp) was inhibited by Mettl3 depletion, while the expression of the cellular fusion-specific gene Atp6v0d2 was upregulated. Mechanistically, Mettl3 knockdown elevated the mRNA stability of Atp6v0d2 and the same result was obtained when the m6A-binding protein YTHDF2 was silenced. Moreover, the phosphorylation levels of key molecules in the MAPK, NF-κB and PI3K-AKT signaling pathways were reduced upon Mettl3 deficiency. Depletion of Mettl3 maintained the retention of Traf6 mRNA in the nucleus and reduced the protein levels of TRAF6. Taken together, our data suggest that METTL3 regulates osteoclast differentiation and function through different mechanisms involving Atp6v0d2 mRNA degradation mediated by YTHDF2 and Traf6 mRNA nuclear export. These findings elucidate the molecular basis of RNA epigenetic regulation in osteoclast development.

Sign in / Sign up

Export Citation Format

Share Document