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The Osteocyte: An Endocrine Cell … and More
Open accessAbstract
Few investigators think of bone as an endocrine gland, even after the discovery that osteocytes produce circulating fibroblast growth factor 23 that targets the kidney and potentially other organs.In fact, until the last few years, osteocytes were perceived by many as passive, metabolically inactive cells.However, exciting recent discoveries have shown that osteocytes encased within mineralized bone matrix are actually multifunctional cells with many key regulatory roles in bone and mineral homeostasis.In addition to serving as endocrine cells and regulators of phosphate homeostasis, these cells control bone remodeling through regulation of both osteoclasts and osteoblasts, are mechanosensory cells that coordinate adaptive responses of the skeleton to mechanical loading, and also serve as a manager of the bone's reservoir of calcium.Osteocytes must survive for decades within the bone matrix, making them one of the longest lived cells in the body.Viability and survival are therefore extremely important to ensure optimal function of the osteocyte network.As we continue to search for new therapeutics, in addition to the osteoclast and the osteoblast, the osteocyte should be considered in new strategies to prevent and treat bone disease.(Endocrine Reviews 34: 658 -690, 2013) I. Introduction II.Osteocyte Differentiation and Embedding III.Morphology of Osteocytes, Their Dendrites, and Lacunocanalicular System IV. Osteocyte Selective Genes/Proteins and Their Potential Functions V. Tools for Studying Osteocytes VI.Osteocyte Mechanosensation and Transduction A. How osteocytes sense loading B. How loading affects osteocyte signaling VII.Osteocytes as Orchestrators of Bone Formation and Resorption VIII.Osteocyte Life, Death, and in Between IX.Osteocytic Perilacunar Remodeling: An Old Concept Rediscovered X.The Osteocyte as an Endocrine Cell XI.Crosstalk Between Osteocytes and Muscle Cells XII.Role of Osteocytes in Disease XIII.
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“Normal bone remodeling is necessary for fracture healing and skeleton adaptation to mechanical use, as well as for calcium homeostasis [15].”
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The RUNX2 Cistrome in Osteoblasts
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The Osteoblast to Osteocyte Transition: Epigenetic Changes and Response to the Vitamin D3Hormone
St. John, H. C., Bishop, K. A., Meyer, M. B., Benkusky, N. A., Leng, N., Kendziorski, C., Bonewald, L. F., & Pike, J. W. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1091 · Cited by 127
Self-citationThe small world of osteocytes: connectomics of the lacuno-canalicular network in bone
Kollmannsberger, P., Kerschnitzki, M., Repp, F., Wagermaier, W., Weinkamer, R., & Fratzl, P. (2017) · Repository for Publications and Research Data (ETH Zurich) · doi:10.3929/ethz-b-000191337 · Cited by 130
The Role of the Osteocyte in Bone and Nonbone Disease
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Self-citationOsteocytic oxygen sensing controls bone mass through epigenetic regulation of sclerostin
Stegen, S., Stockmans, I., Moermans, K., Thienpont, B., Maxwell, P. H., Carmeliet, P., & Carmeliet, G. (2018) · Nature Communications · doi:10.1038/s41467-018-04679-7 · Cited by 126
The osteocyte plays multiple roles in bone remodeling and mineral homeostasis
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Klotho expression in osteocytes regulates bone metabolism and controls bone formation
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The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States
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Changes in the osteocyte lacunocanalicular network with aging
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Deletion of a Single β-Catenin Allele in Osteocytes Abolishes the Bone Anabolic Response to Loading
Javaheri, B., Stern, A. R., Lara, N., Dallas, M., Zhao, H. L., Liu, Y., Bonewald, L. F., & Johnson, M. L. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2064 · Cited by 124
Self-citationEndocrine Crosstalk Between Muscle and Bone
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“Osteocytes have been attributed with multiple roles ranging from mechanosensation to endocrine functions including regulating kidney function, hematopoiesis, and fat metabolism to name a few (for review see Dallas and colleagues((3))).”
BackgroundSelf-citationMolecular Mechanisms of Obesity-Induced Osteoporosis and Muscle Atrophy
Roy, B., Curtis, M. E., Fears, L., Nahashon, S. N., & Fentress, H. M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00439 · Cited by 122
Metadata
- Authors
- Dallas, S. L., Prideaux, M., & Bonewald, L. F.
- Affiliations
- University of Missouri–Kansas City (US)
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2013-04-26
- Volume
- 34
- Issue
- 5
- Pages
- 658-690
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC3785641
- OpenAlex
- W2142302926
- Cited by
- 1,042
- References
- 330
- Citations by year
- 2026: 60 · 2025: 83 · 2024: 60 · 2023: 88 · 2022: 85 · 2021: 113 · 2020: 106 · 2019: 108 · 2018: 89 · 2017: 73 · 2016: 70 · 2015: 69 · 2014: 32 · 2013: 5
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Missouri
- University of Missouri-Kansas City
- National Institutes of Health (AR46798, PO1AG039355, AG039355)
- National Institute on Aging (P01AG039355)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR051517, R56AR051517, P01AR046798, R21AR054449)
- National Center for Research Resources (S10RR027668)
- Army Research Office
- 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 › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- osteocytes, fibroblast growth factor 23, bone mineral homeostasis, phosphate homeostasis, bone remodeling, osteoclast regulation, mechanosensing, mechanotransduction, osteocyte differentiation, osteocyte survival, bone disease
- MeSH terms
- Bone Resorption, Cell Communication, Cell Differentiation, Humans, Osteocytes, Osteogenesis, Cell Death, Muscle Cells, Mechanotransduction, Cellular, Endocrine Cells
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