Syndecan-3 enhances anabolic bone formation through WNT signaling.

FASEB J

Department of Musculoskeletal and Ageing Science (formerly Department of Musculoskeletal Biology), Institute of Life Course and Medical Sciences (formerly Institute of Ageing and Chronic Disease), University of Liverpool, Liverpool, UK.

Published: April 2021

AI Article Synopsis

  • Osteoporosis is a common age-related disorder marked by low bone mass and increased fracture risk, with limited anabolic treatment options.
  • Research shows that Syndecan-3 (Sdc3) boosts new bone formation by enhancing WNT signaling, highlighting its potential for treating osteoporosis.
  • In experiments, overexpressing Sdc3 in osteoblasts improved bone volume in both Sdc3-deficient mice and wild-type mice, suggesting it could be a viable target for developing new bone-building drugs.

Article 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 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 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 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251628PMC
http://dx.doi.org/10.1096/fj.202002024RDOI Listing

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