scholarly journals GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ming Li ◽  
Zhongyu Xie ◽  
Jinteng Li ◽  
Jiajie Lin ◽  
Guan Zheng ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Osteoblast Differentiation ◽  
Bone Repair ◽  
Adipocyte Differentiation ◽  
Bone Fragility ◽  
Treatment Of Osteoporosis ◽  
Repair Ability ◽  
Skeletal Disorder ◽  
Novel Targets

Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. It is still necessary to explore its detailed mechanisms and identify novel targets for the treatment of osteoporosis. Previously, we found that a lncRNA named GAS5 in human could negatively regulate the lipoblast/adipocyte differentiation. However, it is still unclear whether GAS5 affects osteoblast differentiation and whether GAS5 is associated with osteoporosis. Our current research found that GAS5 was decreased in the bones and BMSCs, a major origin of osteoblast, of osteoporosis patients. Mechanistically, GAS5 promotes the osteoblast differentiation by interacting with UPF1 to degrade SMAD7 mRNA. Moreover, a decreased bone mass and impaired bone repair ability were observed in Gas5 heterozygous mice, manifesting in osteoporosis. The systemic supplement of Gas5-overexpressing adenoviruses significantly ameliorated bone loss in an osteoporosis mouse model. In conclusion, GAS5 promotes osteoblast differentiation by targeting the UPF1/SMAD7 axis and protects against osteoporosis.

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 PPARG in osteocytes is essential for sclerostin expression, bone mass, marrow adiposity and TZD-induced bone loss

2020 ◽  
Author(s):  
Sudipta Baroi ◽  
Piotr J. Czernik ◽  
Amit Chougule ◽  
Patrick R. Griffin ◽  
Beata Lecka-Czernik
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Proof Of Concept ◽  
Excellent Correlation ◽  
Transcription Start ◽  
Marrow Fat ◽  
Treatment Of Osteoporosis ◽  
Protein Levels ◽  
Marrow Adiposity ◽  
Specific Deletion

AbstractPPARG role in regulation of osteocyte function is largely unknown. We report that PPARG is essential for sclerostin production, a recently approved target to treat osteoporosis. There is an excellent correlation in osteocytes between Sost/sclerostin and PPARG at the transcript and protein levels, and increased bone mass in mice with osteocyte-specific deletion of PPARG (γOTKO) correlated with increased WNT signaling and bone forming activity of endosteal osteoblasts and decreased marrow fat. The 8 kb sequence upstream of Sost gene transcription start site possesses multiple PPARG binding elements (PPREs) with at least two of them binding PPARG with dynamics reflecting its activation and the levels of Sost transcript and sclerostin protein expression. Older γOTKO female mice are largely protected from TZD-induced bone loss providing proof of concept that PPARG in osteocytes can be pharmacologically targeted. Our study opens the possibility to consider repurposing PPARG as a target for treatment of osteoporosis.

scholarly journals Effects of Estrogen Receptor and Wnt Signaling Activation on Mechanically Induced Bone Formation in a Mouse Model of Postmenopausal Bone Loss

2020 ◽  
Vol 21 (21) ◽  
pp. 8301
Author(s):  
Astrid Liedert ◽  
Claudia Nemitz ◽  
Melanie Haffner-Luntzer ◽  
Fabian Schick ◽  
Franz Jakob ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Postmenopausal Bone Loss ◽  
Paracrine Factors ◽  
Treatment Of Osteoporosis ◽  
Ovariectomized Mice ◽  
Underlying Mechanisms ◽  
Signaling Activation

In the adult skeleton, bone remodeling is required to replace damaged bone and functionally adapt bone mass and structure according to the mechanical requirements. It is regulated by multiple endocrine and paracrine factors, including hormones and growth factors, which interact in a coordinated manner. Because the response of bone to mechanical signals is dependent on functional estrogen receptor (ER) and Wnt/β-catenin signaling and is impaired in postmenopausal osteoporosis by estrogen deficiency, it is of paramount importance to elucidate the underlying mechanisms as a basis for the development of new strategies in the treatment of osteoporosis. The present study aimed to investigate the effectiveness of the activation of the ligand-dependent ER and the Wnt/β-catenin signal transduction pathways on mechanically induced bone formation using ovariectomized mice as a model of postmenopausal bone loss. We demonstrated that both pathways interact in the regulation of bone mass adaption in response to mechanical loading and that the activation of Wnt/β-catenin signaling considerably increased mechanically induced bone formation, whereas the effects of estrogen treatment strictly depended on the estrogen status in the mice.

scholarly journals The Significance of Soy Protein and Soy Bioactive Compounds in the Prophylaxis and Treatment of Osteoporosis

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Sa'eed Bawa
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Soy Protein ◽  
Bone Fragility ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Sufficient Evidence ◽  
Calcium Excretion ◽  
Mineral Density ◽  
Post Menopausal

Osteoporosis is defined as a progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Although bone mass and quality is mainly determined genetically, many other factors, including lifestyle and nutrition also have an impact on bone health. It has been suggested that dietary protein intake may be a risk factor for osteoporosis, and high-protein diets are associated with increased bone loss. Many scientists have examined the relationship between types of protein and urinary calcium excretion, and found that although animal protein was associated with increased urinary calcium excretion, soy protein was not. There is sufficient evidence suggesting soy isoflavones may have potential benefits for bone. Soy protein with naturally occurring phytoestrogens, mainly isoflavones protect against bone loss and synthetic soy ipriflavone in some studies has been shown to favorably affect, but a cause and effect relationship has not been established between the consumption of ipriflavone and maintenance of bone mineral density in post-menopausal women. Therefore it is too early to recommend it as a supplement for this group of women.

scholarly journals Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis

2016 ◽  
Vol 8 (6) ◽  
pp. 225-235 ◽  
Author(s):  
Bente Langdahl ◽  
Serge Ferrari ◽  
David W. Dempster
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
De Novo ◽  
Skeletal Development ◽  
Cathepsin K ◽  
Bone Modeling ◽  
Treatment Of Osteoporosis ◽  
Age Related

The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20–30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.

scholarly journals The Type 2 Cannabinoid Receptor Regulates Bone Mass and Ovariectomy-Induced Bone Loss by Affecting Osteoblast Differentiation and Bone Formation

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2141-2149 ◽  
Author(s):  
Antonia Sophocleous ◽  
Euphemie Landao-Bassonga ◽  
Robert J. van‘t Hof ◽  
Aymen I. Idris ◽  
Stuart H. Ralston
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Osteoblast Differentiation ◽  
Cannabinoid Receptor ◽  
Nodule Formation ◽  
Wild Type

The type 2 cannabinoid receptor (CB2) has been reported to regulate bone mass and bone turnover but the mechanisms responsible are incompletely understood. In this study we investigated the role that the CB2 pathway plays in bone metabolism using a combination of genetic and pharmacological approaches. Bone mass and turnover were normal in young mice with targeted inactivation of CB2 receptor (CB2−/−), but by 12 months of age, they had developed high-turnover osteoporosis with relative uncoupling of bone resorption from bone formation. Primary osteoblasts from CB2−/− mice had a reduced capacity to form bone nodules in vitro when compared with cells from wild-type littermates and also had impaired PTH-induced alkaline phosphatase (ALP) activity. The CB2-selective agonist HU308 stimulated bone nodule formation in wild-type osteoblasts but had no effect in CB2−/− osteoblasts. Further studies in MC3T3-E1 osteoblast like cells showed that HU308 promoted cell migration and activated ERK phosphorylation, and these effects were blocked by the CB2 selective inverse agonist AM630. Finally, HU308 partially protected against ovariectomy induced bone loss in wild-type mice in vivo, primarily by stimulating bone formation, whereas no protective effects were observed in ovariectomized CB2−/− mice. These studies indicate that the CB2 regulates osteoblast differentiation in vitro and bone formation in vivo.

scholarly journals Low bone mass in children and adolescents

2006 ◽  
Vol 50 (4) ◽  
pp. 775-782 ◽  
Author(s):  
João Lindolfo C. Borges ◽  
Cynthia M.A. Brandão
Keyword(s):  
Bone Mass ◽  
Elderly Population ◽  
The Elderly ◽  
Bone Fragility ◽  
Childhood And Adolescence ◽  
Low Bone Mass ◽  
Mass Measurements ◽  
Treatment Of Osteoporosis ◽  
Bone Mass Measurements

Osteoporosis is a disease characterized by low bone mass and micro architectural alterations of bone tissue leading to enhanced bone fragility and increased fracture risk. Although research in osteoporosis has focused mainly on the role of bone loss in the elderly population, it is becoming increasingly clear that the amount of bone that is gained during growth is also an important determinant of future resistance to fractures. Thus, considerable interest is being placed on defining preventive strategies that optimize the gain of bone mass during childhood and adolescence. Knowledge of the determinants accounting for the physiologic and genetic variations in bone accumulation in children will provide the best means toward the early diagnosis and treatment of osteoporosis. This article reviews the techniques available for bone mass measurements in children and the major determinants and diseases influencing bone accretion during childhood and adolescence.

scholarly journals SuO030FK506 ATTENUATES BONE LOSS IN DIABETIC RATS VIA PROMOTING OSTEOBLAST DIFFERENTIATION BUT INHIBITING ADIPOCYTE DIFFERENTIATION

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i628-i629
Author(s):  
Lihua Ni ◽  
Rining Tang ◽  
Linli Lv ◽  
Sisi Wang ◽  
Kaiyun Song ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoblast Differentiation ◽  
Adipocyte Differentiation ◽  
Diabetic Rats

scholarly journals The role of CKIP-1 in osteoporosis development and treatment

2018 ◽  
Vol 7 (2) ◽  
pp. 173-178 ◽  
Author(s):  
X. Peng ◽  
X. Wu ◽  
J. Zhang ◽  
G. Zhang ◽  
G. Li ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Bone Microarchitecture ◽  
Bone Fragility ◽  
Negative Regulation ◽  
Interacting Protein ◽  
Bone Morphogenetic Protein Pathway ◽  
Morphogenetic Protein ◽  
Skeletal Disorder

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment. Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1.

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