The contribution of bone to whole-organism physiology

Karsenty, G.; Ferron, Mathieu

doi:10.1038/nature10763

Cited by 439 publications

(349 citation statements)

References 89 publications

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“…Of these, the only other identified PTP able to bind to the osteoblast IR and respond to isoproterenol treatment similarly to OST-PTP ) is T-cell PTP. This finding further supports the notion that bone is involved in the regulation of glucose metabolism, increasing our understanding of the complex regulation of OC-mediated glucose homoeostasis (Zee et al 2012) (for comprehensive and recent reviews, see Karsenty & Ferron (2012) and Ferron & Lacombe (2014)). …”

Section: Osteocalcinsupporting

confidence: 67%

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Oldknow

MacRae

Farquharson

2015

Journal of Endocrinology

101

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Recent developments in endocrinology, made possible by the combination of mouse genetics, integrative physiology and clinical observations have resulted in rapid and unanticipated advances in the field of skeletal biology. Indeed, the skeleton, classically viewed as a structural scaffold necessary for mobility, and regulator of calcium-phosphorus homoeostasis and maintenance of the haematopoietic niche has now been identified as an important regulator of male fertility and whole-body glucose metabolism, in addition to the classical insulin target tissues. These seminal findings confirm bone to be a true endocrine organ. This review is intended to detail the key events commencing from the elucidation of osteocalcin (OC) in bone metabolism to identification of new and emerging candidates that may regulate energy metabolism independently of OC.Key WordsJournal of Endocrinology (2015) 225, R1-R19

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Section: Osteocalcinsupporting

confidence: 67%

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Oldknow

MacRae

Farquharson

2015

Journal of Endocrinology

101

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“…A growing body of evidence indicates that the skeleton contributes to the regulation of whole-body metabolism (55,56). On one hand, the bone-derived hormone osteocalcin allows the tissue to assist in the regulation of glucose metabolism (17).…”

Section: Discussionmentioning

confidence: 99%

Wnt-Lrp5 Signaling Regulates Fatty Acid Metabolism in the Osteoblast

Frey

Ellis

et al. 2015

Molecular and Cellular Biology

126

104

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fThe Wnt coreceptors Lrp5 and Lrp6 are essential for normal postnatal bone accrual and osteoblast function. In this study, we identify a previously unrecognized skeletal function unique to Lrp5 that enables osteoblasts to oxidize fatty acids. Mice lacking the Lrp5 coreceptor specifically in osteoblasts and osteocytes exhibit the expected reductions in postnatal bone mass but also exhibit an increase in body fat with corresponding reductions in energy expenditure. Conversely, mice expressing a high bone mass mutant Lrp5 allele are leaner with reduced plasma triglyceride and free fatty acid levels. In this context, Wnt-initiated signals downstream of Lrp5, but not the closely related Lrp6 coreceptor, regulate the activation of ␤-catenin and thereby induce the expression of key enzymes required for fatty acid ␤-oxidation. These results suggest that Wnt-Lrp5 signaling regulates basic cellular activities beyond those associated with fate specification and differentiation in bone and that the skeleton influences global energy homeostasis via mechanisms independent of osteocalcin and glucose metabolism. Wnt signaling regulates nearly all aspects of osteoblast function, from initial fate specification (1) to the control of osteoclast differentiation (2). In this pathway, low-density-lipoprotein (LDL)-related receptor 5 (Lrp5) and the closely related Lrp6 participate in the stabilization and activation of the transcription factor ␤-catenin by facilitating the interaction of Wnt ligands with frizzled receptors (3, 4). Osteoblasts express all the components of the Wnt/␤-catenin pathway, and most have now been linked with bone development and maintenance in humans and mouse models (5-7). Mutations in the LRP5 gene, in particular, can result in premature and generalized osteoporosis as in the rare condition osteoporosis pseudoglioma (8) or a high-bone-mass phenotype (9, 10) likely due to an increase in the number of mineralizing osteoblasts (11).Like other metabolically active cells, osteoblasts require a supply of energy-rich molecules to fuel the synthesis, deposition, and mineralization of bone matrix (12). When energy input fails to meet demand, normal bone accrual ceases, a phenomenon that is evident clinically by the arrest of longitudinal bone growth and osteopenia observed in undernourished children and adults (13, 14). Therefore, osteoblasts must possess mechanisms to acquire and regulate the utilization of fuel macromolecules, as well as the ability to communicate energy needs with other tissues.Recent studies have delineated a role for the osteoblast in a bone-pancreas endocrine loop that contributes to the regulation of glucose metabolism, as well as bone acquisition. Insulin receptor signaling in the osteoblast regulates the activity of the osteogenic transcription factor Runx2 and is required for the attainment of a mature phenotype as well as normal postnatal bone acquisition (15). In addition, insulin actions regulate the production and bioavailability of osteocalcin (15, 16), a bone-derived hormone that in ...

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“…The skeleton has long been described as a highly innervated tissue [37] with sensory and autonomic neurons. However, the importance of the nervous system on bone physiology and turnover has begun to be deciphered over the past 15 years [18,33,34,36] and there is now strong data showing that the brain is a powerful regulator of skeletal homeostasis via numerous players and pathways.…”

Section: The Regulation Of Bone Mass By the Cnsmentioning

confidence: 99%

Bone-brain crosstalk and potential associated diseases

Rousseaud

Moriceau

Ramos-Brossier

et al. 2016

Hormone Molecular Biology and Clinical Investigation

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Abstract:Reciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bonederived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

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The contribution of bone to whole-organism physiology

Cited by 439 publications

References 89 publications

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Wnt-Lrp5 Signaling Regulates Fatty Acid Metabolism in the Osteoblast

Bone-brain crosstalk and potential associated diseases

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