Creation and Preliminary Characterization of a Leptin Knockout Rat

Abstract Leptin, a cytokine-like hormone secreted mainly by adipocytes, regulates various pathways centered on food intake and energy expenditure, including insulin sensitivity, fertility, immune system, and bone metabolism. Here, using zinc finger nuclease technology, we created the first leptin knockout rat. Homozygous leptin null rats are obese with significantly higher serum cholesterol, triglyceride, and insulin levels than wild-type controls. Neither gender produced offspring despite of repeated attempts. The leptin knockout rats also have depressed immune system. In addition, examination by microcomputed tomography of the femurs of the leptin null rats shows a significant increase in both trabecular bone mineral density and bone volume of the femur compared with wild-type littermates. Our model should be useful for many different fields of studies, such as obesity, diabetes, and bone metabolism-related illnesses.

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Three-dimensional characterization of trabecular bone mineral density of the proximal ulna using quantitative computed tomography

Journal of Shoulder and Elbow Surgery ◽

10.1016/j.jse.2019.09.040 ◽

2020 ◽

Vol 29 (4) ◽

pp. 755-760

Author(s):

Joseph A. Gil ◽

Katia DaSilva ◽

Eric Johnson ◽

Manuel F. DaSilva ◽

Tyler S. Pidgeon

Keyword(s):

Computed Tomography ◽

Bone Mineral Density ◽

Trabecular Bone ◽

Bone Mineral ◽

Quantitative Computed Tomography ◽

Three Dimensional ◽

Mineral Density ◽

Trabecular Bone Mineral Density ◽

Proximal Ulna

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Inadequate vitamin D status adversely affects trabecular bone mineral density in 14-18 year old adolescents

Bone Abstracts ◽

10.1530/boneabs.6.oc10 ◽

2017 ◽

Author(s):

Taryn Smith ◽

Laura Tripkovic ◽

Camilla Damsgaard ◽

Christian Molgaard ◽

Aine Hennessy ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Trabecular Bone ◽

Bone Mineral ◽

Vitamin D Status ◽

Mineral Density ◽

Trabecular Bone Mineral Density

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Body composition and adipokines influence upon bone mineral density and bone metabolism in renal transplant receivers

Endocrine Abstracts ◽

10.1530/endoabs.70.aep202 ◽

2020 ◽

Author(s):

Anca Matei ◽

Stefana Bilha ◽

Daniela Constantinescu ◽

Petru Cianga ◽

Adrian Covic ◽

...

Keyword(s):

Bone Mineral Density ◽

Body Composition ◽

Renal Transplant ◽

Bone Metabolism ◽

Bone Mineral ◽

Mineral Density

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Changes in bone metabolism associated with exposure to industrial vibration

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2019-59-9-766-767 ◽

2020 ◽

pp. 766-766

Author(s):

A. V. Sukhova ◽

E. N. Kryuchkova

Keyword(s):

Bone Mineral Density ◽

Alkaline Phosphatase ◽

Bone Resorption ◽

Bone Formation ◽

Bone Metabolism ◽

Biochemical Markers ◽

Mineral Density ◽

Local Vibration ◽

Markers Of Bone Formation

The influence of general and local vibration on bone remodeling processes is investigated. The interrelations between the long - term exposure of industrial vibration and indicators of bone mineral density (T-and Z-criteria), biochemical markers of bone formation (osteocalcin, alkaline phosphatase) and bone resorption (ionized calcium, calcium/creatinine) were established.

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Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor a and b Pathways*

10.31234/osf.io/592mt ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Bone Mineral Density ◽

Estrogen Receptor ◽

Bone Loss ◽

Bone Turnover ◽

Bone Mineral ◽

Female Rats ◽

Wild Type ◽

Mineral Density ◽

Transgenic Rats ◽

Estrogen Sensitivity

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

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Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530318666181102115106 ◽

2019 ◽

Vol 19 (3) ◽

pp. 259-273 ◽

Cited By ~ 3

Author(s):

Neelam Kaushal ◽

Divya Vohora ◽

Rajinder K Jalali ◽

Sujeet Jha

Keyword(s):

Risk Factors ◽

Bone Mineral Density ◽

Uric Acid ◽

Bone Metabolism ◽

Serum Uric Acid ◽

Bone Mineral ◽

Molecular Mechanisms ◽

Association Studies ◽

Mineral Density ◽

Age Related

Background And Objective:Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA).Discussion:Uric acid’s antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1.Conclusion:In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.

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