Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation
Top Cited Papers
- 25 August 2005
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 19 (13), 1842-1844
- https://doi.org/10.1096/fj.05-4221fje
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.Keywords
Funding Information
- Medical Research Council
- National Osteoporosis Society
- European Commission (LSHM‐CT‐2003‐503020)
This publication has 30 references indexed in Scilit:
- Upregulation of Osteopontin by Osteocytes Deprived of Mechanical Loading or OxygenJournal of Bone and Mineral Research, 2005
- Periosteum: biology, regulation, and response to osteoporosis therapiesBone, 2004
- Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formationBone, 2004
- The osteocyteThe International Journal of Biochemistry & Cell Biology, 2004
- Sclerostin Is a Novel Secreted Osteoclast-derived Bone Morphogenetic Protein Antagonist with Unique Ligand SpecificityPublished by Elsevier BV ,2003
- Bone Resorption by OsteoclastsScience, 2000
- Mechanical Loading Stimulates Bone Formation by Reactivation of Bone Lining Cells in 13‐Week‐Old RatsJournal of Bone and Mineral Research, 1998
- Cortical Remodeling Following Suppression of Endogenous Estrogen with Analogs of Gonadotrophin Releasing HormoneJournal of Bone and Mineral Research, 1997
- A Stochastic Analysis of Iliac Trabecular Bone DynamicsClinical Orthopaedics and Related Research, 1986
- Sclerosteosis — An autosomal recessive disorderClinical Genetics, 1977