Cited by 966Bone Metabolism and DiseasesBone health and osteoporosis researchBone and Dental Protein Studies

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Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation

Poole, Kenneth E. S., Van Bezooijen, Rutger L., Loveridge, Nigel, Hamersma, Herman, Papapoulos, Socrates E., Löwik, Clemens W., Reeve, Jonathan·2005·The FASEB Journal

DOI 10.1096/fj.05-4221fje

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Abstract

Osteocytes are the most abundant cells in bone and are ideally located to influence bone turnover through their syncytial relationship with surface bone cells. Osteocyte‐derived signals have remained largely enigmatic, but it was recently reported that human osteocytes secrete sclerostin, an inhibitor of bone formation. Absent sclerostin protein results in the high bone mass clinical disorder sclerosteosis. Here we report that within adult iliac bone, newly embedded osteocytes were negative for sclerostin staining but became positive at or after primary mineralization. The majority of mature osteocytes in mineralized cortical and cancellous bone was positive for sclerostin with diffuse staining along dendrites in the osteocyte canaliculi. These findings provide for the first time in vivo evidence to support the concept that osteocytes secrete sclerostin after they become embedded in a mineralized matrix to limit further bone formation by osteoblasts. Sclerostin did not appear to influence the formation of osteocytes. We propose that sclerostin production by osteocytes may regulate the linear extent of formation and the induction or maintenance of a lining cell phenotype on bone surfaces. In doing so, sclerostin may act as a key inhibitory signal governing skeletal microarchitecture.

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Self-citation

Authors: Poole, K. E. S., Van Bezooijen, R. L., Loveridge, N., Hamersma, H., Papapoulos, S. E., Löwik, C. W., & Reeve, J.
Affiliations: University of Cambridge (GB)
Department of Endocrinology and Metabolic Diseases Leiden University Medical Centre Leiden Netherlands
South Africa
Leiden University (NL)
ORCID: Poole, Kenneth E. S.
Loveridge, Nigel
Hamersma, Herman
Papapoulos, Socrates E.
Löwik, Clemens W.
Reeve, Jonathan
Venue: The FASEB Journal
Publisher: Wiley
Published: 2005-08-25
Volume: 19
Issue: 13
Pages: 1842-1844
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.05-4221fje
OpenAlex: W1970864109
Cited by: 965
References: 34
Citations by year: 2026: 21 · 2025: 28 · 2024: 32 · 2023: 39 · 2022: 38 · 2021: 45 · 2020: 74 · 2019: 63 · 2018: 55 · 2017: 53 · 2016: 66 · 2015: 67 · 2014: 55 · 2013: 62 · 2012: 63
FWCI: 10.29
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Funders: Medical Research Council
National Osteoporosis Society
European Commission (LSHM‐CT‐2003‐503020)
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
Keywords: sclerostin, osteocytes, bone formation inhibition, sclerosteosis, osteoblasts, bone mineralization, bone lining cells, bone turnover
MeSH terms: Aged, Alkaline Phosphatase, Antibodies, Monoclonal, Biopsy, Bone and Bones, Bone Development, Bone Diseases, Developmental, Bone Resorption, Cell Differentiation, Coloring Agents, Female, Genetic Markers, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Male, Microscopy, Fluorescence, Middle Aged, Models, Biological, Osteoblasts, Osteocytes, Osteogenesis, RNA, Messenger, Time Factors, Tolonium Chloride, Signal Transduction, Bone Remodeling, Bone Morphogenetic Proteins, Adaptor Proteins, Signal Transducing

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Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation

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