Skeletal energy homeostasis: a paradigm of endocrine discovery

Suchacki, Karla J; Roberts, Fiona; Lovdel, Andrea; Farquharson, Colin; Morton, Nik; MacRae, Vicky; Cawthorn, William P.

doi:10.1530/joe-17-0147

Cited by 40 publications

(35 citation statements)

References 93 publications

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“…Adipose tissue exists in multiple anatomical locations, most of which are outside of the skeleton; however, bone has been shown to influence global energy metabolism through release of endocrine factors such as osteocalcin by osteoblast lineage cells (reviewed by Wei & Karsenty 2015, Suchacki et al 2017. The concept that sclerostin and energy metabolism could be linked reflects several observations including positive associations between serum sclerostin and metabolic parameters such as fat mass and type 2 diabetes (Amrein et al 2012, Clarke & Drake 2013.…”

Section: Adipocytesmentioning

confidence: 99%

Novel actions of sclerostin on bone

Holdsworth

Roberts

2019

Journal of Molecular Endocrinology

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The discovery that two rare autosomal recessive high bone mass conditions were caused by the loss of sclerostin expression prompted studies into its role in bone homeostasis. In this article, we aim to bring together the wealth of information relating to sclerostin in bone though discussion of rare human disorders in which sclerostin is reduced or absent, sclerostin manipulation via genetic approaches and treatment with antibodies that neutralise sclerostin in animal models and in human. Together, these findings demonstrate the importance of sclerostin as a regulator of bone homeostasis and provide valuable insights into its biological mechanism of action. We summarise the current state of knowledge in the field, including the current understanding of the direct effects of sclerostin on the canonical WNT signalling pathway and the actions of sclerostin as an inhibitor of bone formation. We review the effects of sclerostin, and its inhibition, on bone at the cellular and tissue level and discuss new findings that suggest that sclerostin may also regulate adipose tissue. Finally, we highlight areas in which future research is expected to yield additional insights into the biology of sclerostin.

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Section: Adipocytesmentioning

confidence: 99%

Novel actions of sclerostin on bone

Holdsworth

Roberts

2019

Journal of Molecular Endocrinology

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“…Bone remodeling involves two distinct processes, removal of old or damaged bone by osteoclasts and its subsequent replacement with new bone by osteoblasts. 3 , 4 Osteoblasts differentiate from mesenchymal stem cells (MSCs) and comprise 5% of all bone cells, which are responsible for the synthesis of type I collagen and the deposition of mineralized matrix to facilitate the formation of bone. 5 , 6 Furthermore, osteoblasts give rise to terminally differentiated osteocytes, the most abundant skeletal cell, which comprise 90% of total bone cells and are embedded in the bone matrix.…”

Section: Introductionmentioning

confidence: 99%

Paracrine and endocrine actions of bone—the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts

et al. 2018

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The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes, and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin (SOST) that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influenceaA osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or “osteokines” from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin (OCN) secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2 (LCN2) is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain. We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.

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“…The skeleton is considered to be an essential support organ that protects vital organs, stores minerals, and provides a mechanical bracket for body and movement (Han et al, 2018). Osteoblast-mediated bone formation and osteoclast-mediated bone resorption maintain a dynamic balance through signaling proteins, such as asephrin-Eph, which bone remodeling process occurs throughout the lifespan to ensure the integrity of the skeleton and its multiple functions (Zhao et al, 2006;Suchacki et al, 2017). It has also been proposed that osteocytes play essential roles in bone remodeling by affecting the activities of osteoblasts and osteoclasts (Tatsumi et al, 2007).…”

Section: The Roles Of Bone-derived Exosomes In Skeletal Metabolismmentioning

confidence: 99%

The Role of Bone-Derived Exosomes in Regulating Skeletal Metabolism and Extraosseous Diseases

Lyu

Xiao

Guo

et al. 2020

Front. Cell Dev. Biol.

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Bone-derived exosomes are naturally existing nano-sized extracellular vesicles secreted by various cells, such as bone marrow stromal cells, osteoclasts, osteoblasts, and osteocytes, containing multifarious proteins, lipids, and nucleic acids. Accumulating evidence indicates that bone-derived exosomes are involved in the regulation of skeletal metabolism and extraosseous diseases through modulating intercellular communication and the transfer of materials. Following the development of research, we found that exosomes can be considered as a potential candidate as a drug delivery carrier thanks to its ability to transport molecules into targeted cells with high stability, safety, and efficiency. This review aims to discuss the emerging role of bone-derived exosomes in skeletal metabolism and extraosseous diseases as well as their potential role as candidate biomarkers or for developing new therapeutic strategies.

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Skeletal energy homeostasis: a paradigm of endocrine discovery

Cited by 40 publications

References 93 publications

Novel actions of sclerostin on bone

Novel actions of sclerostin on bone

Paracrine and endocrine actions of bone—the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts

The Role of Bone-Derived Exosomes in Regulating Skeletal Metabolism and Extraosseous Diseases

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