Syndecan‐3 enhances anabolic bone formation through WNT signaling

• DOI: 10.1096/fj.202002024r
• Publication Date: 2021-03-26T15:23:09Z
• Authors: Francesca Manuela...; Andrew Butcher; Addolorata Pisconti; Blandine Poulet; Amanda Prior; Gemma Charlesworth; Catherine Sperinck; Michele Scotto di...; Ke Liu; George Bou‐Gharios; Robert Jurgen van...; Anna Daroszewska
• Keywords: Syndecan 1; Bone Formation

Abstract Osteoporosis is the most common age‐related metabolic bone disorder, which characterized by low mass and deterioration in architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts form new restore structure, however, anabolic therapeutics are few their use time restricted. Here, we report that Syndecan‐3 increases formation through enhancement WNT signaling osteoblasts. Young adult Sdc3 −/− mice have volume, reduced formation, increased marrow adipose tissue, fragility, blunted response mechanical loading. This premature osteoporosis‐like phenotype due delayed osteoblast maturation impaired function, contributing osteoclast‐mediated resorption. Indeed, overexpressing using Col1a1 promoter rescues volume mice, also WT mice. Mechanistically, SDC3 enhances canonical stabilization Frizzled 1, making an attractive target novel drug development.