High affinity leptin receptors are present in human mesenchymal stem cells (MSCs) derived from control and osteoporotic donors

Hess, Rodrigo; Pino, Ana María; Rı́os, Susana; Fernández, Mireya; Rodríguez, Juan ́Pablo

doi:10.1002/jcb.20330

Cited by 73 publications

(68 citation statements)

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“…Leptin activity on immortalized stroma cells from human bone marrow increased their differentiation to osteoblasts, while it inhibited their differentiation to adipocytes, suggesting a role for leptin in bone metabolism (Thomas et al 1999). Previously, we have demonstrated the presence of membrane leptin receptors through early hMSCs differentiation, as well as its direct protective effect on their OS differentiation process (Hess et al 2005). Therefore, from our results it may be suggested that part of the protective influence of leptin on bone tissue may result from its effect on aromatase activity during early differentiation of hMSCs.…”

Section: Discussionmentioning

confidence: 94%

“…Several in vitro studies indicate that stromal cells are responsive to leptin, which increases proliferation, differentiation to osteoblastic lineage and the number of mineralized nodules (Takahashi et al 1997, Thomas et al 1999, Reseland et al 2001, but inhibits differentiation to adipocytes (Thomas et al 1999, Hess et al 2005. These observations suggest that leptin may participate in the regulation of bone mass, but the mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…These observations suggest that leptin may participate in the regulation of bone mass, but the mechanism remains unclear. We have recently demonstrated the presence of high affinity leptin receptors associated with the cell membranes of hMSCs and a direct protective action of leptin on osteogenesis (Hess et al 2005). On the other hand, vitamin D deficiency is an important risk factor for bone mass loss.…”

Section: Introductionmentioning

confidence: 99%

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Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin

Pino¹,

Rodríguez²,

Rı́os³

et al. 2006

Journal of Endocrinology

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Human mesenchymal stem cells (hMSCs) are multipotent cells present in bone marrow, which differentiate into osteoblasts and adipocytes, among other lineages. Oestrogens play a critical role in bone metabolism; its action may affect the adipocyte to osteoblast ratio in the bone marrow. In hMSCs, oestrogens are synthesized from C19 steroids by the enzyme aromatase cytochrome P450. In this study, we assessed whether aromatase enzymatic activity varied through early osteogenic (OS) and adipogenic (AD) differentiation. Also, we studied the effect of leptin and 1,25 dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) on aromatase cell activity. Finally, we analysed whether conditions that modify oestrogen generation by cells affected hMSCs differentiation. For these purposes, hMSCs derived from postmenopausal women (65-86 years old) were cultured under basal, OS or AD conditions, in the presence or the absence of leptin and 1,25(OH) 2 D 3 . Aromatase activity was measured by the tritiated water release assay and by direct measurement of steroids synthesized from 3 H-labelled androstenedione or testosterone. Our results showed that different OS and AD patterns of aromatase activity developed during the first period of differentiation (up to 7 days). A massive and sharp surge of aromatase activity at 24 h characterized early OS differentiation, while increased but constant aromatase activity was increased through adipogenesis. Both leptin and vitamin D increased aromatase activity during osteogenesis, but not during adipogenesis; finally, we showed that favourable aromatase substrates concentration restrained MSCs adipogenesis but improved osteogenesis. Thus, it could be inferred that a high and early increase of local oestrogen concentration in hMSCs affects their commitment either restraining AD or facilitating OS differentiation, or both.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin

Pino¹,

Rodríguez²,

Rı́os³

et al. 2006

Journal of Endocrinology

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“…The ultimate fate of multipotent mesenchymal stem cells first located in bone marrow are potentially adipogenic, osteogenic, and even myogenic (Mo et al, 2016), and contain highly functional leptin receptors (Hess et al, 2005). HDL, traditionally inversely linked to adipose tissue and BMI, is also shown to correlate with non-adipose components of the body such as skeletal mass (Pietrobelli et al, 1999.).…”

Section: Discussionmentioning

confidence: 99%

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Mosher¹,

Melton²,

Stapleton³

et al. 2016

Human Biology

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DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA which are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process.Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative function includes regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism and Pre-print version. Visit http://digitalcommons.wayne.edu/humbiol/ after publication to acquire the final version.reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examines the significance of variation in DNA methylation patterns along the leptin core promoter in four populations and uses biomarkers reflecting leptin's functional process in two of those populations to investigate the relevance of the ethnic variation identified in the DNA methylation. Those two populations are the Western Buryats of Siberia and the Mennonites of Central Kansas.LEP's core promoter region contains both the C/EBPα transcription binding site (TBS) which tempers the final step in adipocyte maturity and capacity to synthesize leptin and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, with others suggesting tissue-specific methylation variation at this region. We hypothesize that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers which reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system and anthropometric measures.A distinct and consistent overall pattern of differential DNA methylation across seven CpG sites of LEP core promoter is documented in all ethnicities and both sexes in our combined analyses of 313 individuals. This pattern replicates those identified in previous studies, thus suggesting a conserved core promoter region across populations. The second analyses in two of the four ...

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“…In osteoporotic BM of postmenopausal women, the levels of leptin and adiponectin were significantly lower [107]. Besides, the affinity of leptin receptors on osteoporotic MSCs is also lower [108] indicating decreased leptin signal activity. However, the action of leptin on the bone appears to have both positive and negative consequences and is not fully understood.…”

Section: Excessive Adipose Tissuementioning

confidence: 95%

The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis

Liu

Zuo

et al. 2016

Aging and disease

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ABSTRACT:In the adult bone marrow, osteoblasts and adipocytes share a common precursor called mesenchymal stem cells (MSCs). The plasticity between the two lineages has been confirmed over the past decades, and has important implications in the etiology of bone diseases such as osteoporosis, which involves an imbalance between osteoblasts and adipocytes. The commitment and differentiation of bone marrow (BM) MSCs is tightly controlled by the local environment that maintains a balance between osteoblast lineage and adipocyte. However, pathological conditions linked to osteoporosis can change the BM microenvironment and shift the MSC fate to favor adipocytes over osteoblasts, and consequently decrease bone mass with marrow fat accumulation. This review discusses the changes that occur in the BM microenvironment under pathological conditions, and how these changes affect MSC fate. We suggest that manipulating local environments could have therapeutic implications to avoid bone loss in diseases like osteoporosis.

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High affinity leptin receptors are present in human mesenchymal stem cells (MSCs) derived from control and osteoporotic donors

Cited by 73 publications

References 46 publications

Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin

Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis

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