Cited by 1,123Bone Metabolism and DiseasesBone health and osteoporosis researchAlkaline Phosphatase Research Studies

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Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism

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Ferron, Mathieu, Wei, Jianwen, Yoshizawa, Tatsuya, Del Fattore, Andrea, DePinho, Ronald A., Teti, Anna, Ducy, Patricia, Karsenty, Gerard·2010·Cell

DOI 10.1016/j.cell.2010.06.003PMC PMC2910411

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Abstract

The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism.

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Ferron, M., Hinoi, E., Karsenty, G., and Ducy, P. (2008). Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc. Natl. Acad. Sci. USA 105, 5266–5270. · DOI · Paper page

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Authors: Ferron, M., Wei, J., Yoshizawa, T., Del Fattore, A., DePinho, R. A., Teti, A., Ducy, P., & Karsenty, G.
Affiliations: Columbia University (US)
Harvard University (US)
University of L'Aquila (IT)
ORCID: Ferron, Mathieu
Wei, Jianwen
Yoshizawa, Tatsuya
DePinho, Ronald A.
Teti, Anna
Ducy, Patricia
Venue: Cell
Publisher: Elsevier BV
Published: 2010-07
Volume: 142
Issue: 2
Pages: 296-308
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2010.06.003
PMC: PMC2910411
OpenAlex: W1971400919
Cited by: 1,123
References: 49
Citations by year: 2026: 30 · 2025: 47 · 2024: 50 · 2023: 41 · 2022: 43 · 2021: 62 · 2020: 84 · 2019: 65 · 2018: 73 · 2017: 89 · 2016: 75 · 2015: 100 · 2014: 76 · 2013: 84 · 2012: 87
FWCI: 37.16
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1148 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078042)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR045548)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Keywords: insulin signaling, osteoblasts, osteocalcin, bone remodeling, bone resorption, glucose homeostasis, energy metabolism, uncarboxylated osteocalcin, decarboxylation, osteoclasts, feed-forward loop
MeSH terms: Animals, Cells, Cultured, Energy Metabolism, Extracellular Matrix, Glucose, Humans, Insulin, Mice, Inbred C57BL, Osteoblasts, Signal Transduction, Osteocalcin, Bone Remodeling, Mice

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Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism

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