Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1

Huang, Shu; Kaw, Meenakshi; Harris, Mark; Ebraheim, Nabil A.; McInerney, Marcia F.; Najjar, Sonia M.; Lecka‐Czernik, Beata

doi:10.1016/j.bone.2009.12.020

Cited by 56 publications

(47 citation statements)

References 27 publications

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“…In vivo, Kawashima et al (17) found evidence supporting increased osteoclastogenesis in the diabetic bone microenvironment (17). In vitro, Huang et al (18) reported that an elevated insulin environment negatively regulated osteoclast differentiation and the expression of RANK and c-fos (18), and these results were corroborated by a study by Dienelt and zur Nieden (19). The data from the present study suggest that bone resorption was impaired in the T2DM model due to impaired osteoclast function.…”

Section: Discussionsupporting

confidence: 80%

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Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes

Dong

Huang

et al. 2014

Molecular Medicine Reports

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Abstract. The effect of type 2 diabetes mellitus (T2DM) on bone is controversial. Therefore, the present study investigated whether T2DM causes osteoporosis and explored the underlying mechanisms involved in this process. The effects of T2DM on bone physiology were analyzed in a mouse model of T2DM; KK/Upj-Ay/J (KK-Ay) mice develop diabetes after 8 weeks and exhibit stable diabetes symptoms and signs after 10 weeks when fed a KK-Ay mouse maintenance fodder. Diabetic mice exhibited hyperglycemia, hyperinsulinemia and increased body and fat pad weight in comparison with C57BL/6 non-diabetic mice. Furthermore, diabetic mice demonstrated low bone weight and bone mineral density in the femur, tibia and fifth lumbar vertebra. Using von Kossa and tartrate-resistant acid phosphatase (TRAP) staining, alkaline phosphatase and TRAP activity analyses and gene profiling it was demonstrated that osteoblastogenesis and osteoclastogenesis were impaired in diabetic mice. To evaluate the bone biomechanics, the ultimate load of the bone was analyzed. It was found that the ultimate load of the tibia in diabetic mice was lower than that in the controls. The results from the present study suggest that bone metabolism is impaired in T2DM, resulting in decreased osteoblastogenesis, osteoclastogenesis and bone mass.

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Section: Discussionsupporting

confidence: 80%

“…environment is a negative factor for bone formation (18). Therefore, for these reasons, obesity is a promoting factor for osteoporosis in T2DM.…”

Section: A B C Dmentioning

confidence: 99%

Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes

Dong

Huang

et al. 2014

Molecular Medicine Reports

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“…Insulin affects bone remodeling by decreasing both bone formation and resorption (Huang et al 2010). High level of insulin affects the recruitment and differentiation of osteoclast by impairing the RANKL signaling pathway.…”

Section: Effect Of Insulin Resistance On Bone In Pcos Womenmentioning

confidence: 99%

“…High level of insulin affects the recruitment and differentiation of osteoclast by impairing the RANKL signaling pathway. Huang and coworkers studied that the addition of insulin to the ex vivo osteoclast cell culture decreased the number of TRAP-positive cells (Huang et al 2010). Therefore, it is possible that high level of insulin in women suffering from PCOD may bind to insulin receptor in osteoblast and reduce bone formation and can also affect bone resorption.…”

Section: Effect Of Insulin Resistance On Bone In Pcos Womenmentioning

confidence: 99%

Hormonal alterations in PCOS and its influence on bone metabolism

Krishnan¹,

Muthusami²

2017

Journal of Endocrinology

129

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According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women.

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“…These mice are characterized by high bone mass due to attenuated bone resorption as a result, at least in part, of insulin's negative effect on osteoclasts. (68) However, there are diabesity models associated with both pronounced hyperglycemia and obesity, including New Zealand Obese (NZO/HlLt and NZO/HlBomDife), yellow agouti A vy /a, and the TALLYHO/JngJ mouse. The yellow agouti and TALLYHO/JngJ mice may be particularly useful in future studies because in these models the onset of T2D occurs early, thereby paralleling the rising epidemic of T2D in adolescence.…”

mentioning

confidence: 99%

Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights

Lecka‐Czernik

Rosen

2015

Journal of Bone and Mineral Research

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Skeletal complications have recently been recognized as another of the several comorbidities associated with diabetes. Clinical studies suggest that disordered glucose and lipid metabolism have a profound effect on bone. Diabetes-related changes in skeletal homeostasis result in a significant increased risk of fractures, although the pathophysiology may differ from postmenopausal osteoporosis. Efforts to understand the underlying mechanisms of diabetic bone disease have focused on the direct interaction of adipose tissue with skeletal remodeling and the potential influence of glucose utilization and energy uptake on these processes. One aspect that has emerged recently is the major role of the central nervous system in whole-body metabolism, bone turnover, adipose tissue remodeling, and beta cell secretion of insulin. Importantly, the skeleton contributes to the metabolic balance inherent in physiologic states. New animal models have provided the insights necessary to begin to dissect the effects of obesity and insulin resistance on the acquisition and maintenance of bone mass. In this Perspective, we focus on potential mechanisms that underlie the complex interactions between adipose tissue and skeletal turnover by focusing on the clinical evidence and on preclinical studies indicating that glucose intolerance may have a significant impact on the skeleton. In addition, we raise fundamental questions that need to be addressed in future studies to resolve the conundrum associated with glucose intolerance, obesity, and osteoporosis. © 2015 American Society for Bone and Mineral Research. KEY WORDS: BONE-FAT INTERACTIONS; SYSTEMS BIOLOGY; BONE INTERACTORS; CELL/TISSUE SIGNALING; TRANSCRIPTION FACTORS; DISEASES AND DISORDERS OF/RELATED TO BONE Clinical Insight Into the Effect of Disordered Glucose and Lipids Homeostasis on BoneD iabetes mellitus (DM) can be considered a disease of intracellular glucose starvation in muscle and fat, due to either lack of insulin (Type 1 [T1D]) or impaired insulin action (Type 2 [T2D]). Both types of DM are associated with an increase in fractures; however, the skeletal phenotype is very different. T1D patients have reduced bone mineral density (BMD), due to insulin and amylin deficiency, whereas T2D patients have either normal or high BMD. T2D is a disease of disordered energy storage as well as glucose intolerance and altered bone strength. Its prevalence is high and not abating. In the United States, 29.1 million people-9.3% of the population-have diabetes; among them, nearly 60% are characterized as obese (http://www.cdc.gov). Insulin resistance is a characteristic feature of T2D in liver, muscle, and fat, leading to glucose intolerance, elevated cardiometabolic risk factors (eg, low-density lipoprotein [LDL] cholesterol), and excess hepatic glucose output. Visceral adipocytes, in particular, are large and surrounded by fibrous and inflammatory elements.In clinical medicine a major paradox is the relationship of obesity to the skeleton. Obese individuals tend to have higher...

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Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1

Cited by 56 publications

References 27 publications

Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes

Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes

Hormonal alterations in PCOS and its influence on bone metabolism

Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights

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