Johnson de Sousa Brito, Francesca Manuela, Butcher, Andrew, Pisconti, Addolorata, Poulet, Blandine, Prior, Amanda, Charlesworth, Gemma, Sperinck, Catherine, Scotto di Mase, Michele, Liu, Ke, Bou-Gharios, George et al (show 2 more authors)
(2021)
Syndecan-3 enhances anabolic bone formation through WNT signaling.
FASEB JOURNAL, 35 (4).
e21246-.
Abstract
Osteoporosis is the most common age-related metabolic bone disorder, which is characterized by low bone mass and deterioration in bone architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts to form new bone and restore bone structure, however, anabolic therapeutics are few and their use is time restricted. Here, we report that Syndecan-3 increases new bone formation through enhancement of WNT signaling in osteoblasts. Young adult Sdc3<sup>-/-</sup> mice have low bone volume, reduced bone formation, increased bone marrow adipose tissue, increased bone fragility, and a blunted anabolic bone formation response to mechanical loading. This premature osteoporosis-like phenotype of Sdc3<sup>-/-</sup> mice is due to delayed osteoblast maturation and impaired osteoblast function, with contributing increased osteoclast-mediated bone resorption. Indeed, overexpressing Sdc3 in osteoblasts using the Col1a1 promoter rescues the low bone volume phenotype of the Sdc3<sup>-/-</sup> mice, and also increases bone volume in WT mice. Mechanistically, SDC3 enhances canonical WNT signaling in osteoblasts through stabilization of Frizzled 1, making SDC3 an attractive target for novel bone anabolic drug development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | bone, frizzled, osteoblast, Syndecan‐, 3, WNT |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Apr 2021 10:00 |
| Last Modified: | 18 Jan 2023 22:54 |
| DOI: | 10.1096/fj.202002024R |
| Open Access URL: | https://faseb.onlinelibrary.wiley.com/doi/10.1096/... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3118422 |
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