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- Jensen, Vivi F.H., et al.
(author)
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Changes in bone mass associated with obesity and weight loss in humans : Applicability of animal models
- 2021
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In: Bone. - : Elsevier BV. - 8756-3282. ; 145
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Research review (peer-reviewed)abstract
- The implications of obesity and weight loss for human bone health are not well understood. Although the bone changes associated with weight loss are similar in humans and rodents, that is not the case for obesity. In humans, obesity is generally associated with increased bone mass, an outcome which is exacerbated by advanced age and menopause. In rodents, by contrast, bone mass decreases in proportion to severity and duration of obesity, and is influenced by sex, age and mechanical load. Despite these discrepancies, rodents are frequently used to model the situation in humans. In this review, we summarise the existing knowledge of the effects of obesity and weight loss on bone mass in humans and rodents, focusing on the translatability of findings from animal models. We then describe how animal models should be used to broaden the understanding of the relationship between obesity, weight loss, and skeletal health in humans. Specifically, we highlight the aspects of study design that should be considered to optimise translatability of the rodent models of obesity and weight loss. Notably, the sex, age, and nutritional status of the animals should ideally match those of interest in humans. With these caveats in mind, and depending on the research question asked, our review underscores that animal models can provide valuable information for obesity and weight-management research.
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| 2. |
- Sanchez-Duffhues, Gonzalo, et al.
(author)
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Bone morphogenetic protein receptors : Structure, function and targeting by selective small molecule kinase inhibitors
- 2020
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In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 138
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Research review (peer-reviewed)abstract
- Bone morphogenetic proteins (BMPs) are secreted cytokines that control the fate and function of many different cell types. They exert their cellular responses via heteromeric complexes of specific BMP type I and type II serine/threonine kinase receptors, e.g. BMPRIA and BMPRII. Three type II and four type I receptors, also termed activin receptor-like kinases (ALKs), have been identified. The constitutively active type II kinase phosphorylates the type I receptor, which upon activation initiates intracellular signaling by phosphorylating SMAD effectors. Auxiliary cell surface receptors without intrinsic enzymatic motifs, such as Endoglin and Repulsive guidance molecules (RGM), can fine-tune signaling by regulating the interaction of the BMP ligands with the BMPRs. The functional annotation of the BMPR encoding genes has helped to understand underlying mechanisms of diseases in which these genes are mutated. Loss of function mutations in BMPRII, Endoglin or RGMc are causally linked to pulmonary arterial hypertension, hereditary hemorrhagic telangiectasia and juvenile hemochromatosis, respectively. In contrast, gain of function mutations in ACVR1, encoding ALK2, are linked to Fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. Here, we discuss BMPR identification, structure and function in health and disease. Moreover, we highlight the therapeutic promise of small chemical compounds that act as selective BMPR kinase inhibitors to normalize overactive BMPR signaling.
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