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sclerostin (SOST)
Function:
- bone homeostasis (putative)
- osteocyte-derived inhibitor of osteoblast activity [3]
Structure:
1) belongs to the sclerostin family
2) contains 1 CTCK domain (C-terminal cystine knot-like domain)
Compartment: secreted
Alternative splicing: named isoforms=2
Expression:
- widely expressed at low levels
- highest expression in bone, cartilage, kidney, liver, bone marrow, & primary osteoblasts differentiated for 21 days (osteocytes)
Physiology:
- osteocytes make sclerostin [4]
- sclerostin generally inhibits bone formation
- when osteocytes sense bone-loading activities, sclerostin secretion diminishes, allowing for increased bone formation [4]
Pathology:
- defects in SOST are assosiated with sclerosteosis
Pharmacology:
- romosozumab a monoclonal antibody that binds to sclerostin & increases bone formation may be useful for treatment of osteoporosis [3]
General
glycoprotein
secreted protein
Properties
SIZE: MW = 24 kD
entity length = 213 aa
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-23}
N-glycosylation site {N53}
C-terminal cystine knot {82-172}
N-glycosylation site {N175}
Database Correlations
OMIM correlations
MORBIDMAP 605740
UniProt Q9BQB4
Pfam PF05463
References
- UniProt :accession Q9BQB4
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=SOST
- McClung MR et al
Romosozumab in Postmenopausal Women with Low Bone Mineral Density.
N Engl J Med. Jan 1, 2014
PMID: 24382002
http://www.nejm.org/doi/full/10.1056/NEJMoa1305224
- Becker CB
Sclerostin Inhibition for Osteoporosis - A New Approach.
PMID: 24382003
http://www.nejm.org/doi/full/10.1056/NEJMe1315500
- Misra M
Which Exercise Is Best for Bone Health?
Medscape. Nov 14, 2022
https://www.medscape.com/viewarticle/983792