Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation
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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Osteocyte markers including dentine matrix protein 1 (DMP1) and sclerostin are highly expressed in mature osteocytes.
“On the other hand, osteocyte markers including dentine matrix protein 1 (DMP1) and sclerostin are highly expressed [8, 62–64].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [63]
Sclerostin is a product of the SOST gene and a negative regulator of bone formation by antagonizing Lrp5 actions in osteoblasts.
“Sclerostin is a product of the SOST gene and is known to be a negative regulator of bone formation, by antagonizing in osteoblasts the actions of Lrp5, a key receptor of the Wnt/β-catenin signaling pathway [63].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [63]
Sclerostin decreases bone formation by repressing osteoblast differentiation and proliferation.
“Another endogenous Wnt antagonist secreted almost exclusively by osteocytes, sclerostin, decreases bone formation by repressing osteoblast differentiation and proliferation [[92], [93], [94]].”
From Emerging role of liver-bone axis in osteoporosis (2024) · cites this paper as [92]
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- 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
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2005-08-25
- Volume
- 19
- Issue
- 13
- Pages
- 1842-1844
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- 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
- 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
- Health Sciences › Medicine › Rheumatology › 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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