RSPO3 is Important for Trabecular Bone and Fracture Risk in Mice and Humans

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Aug 14

PMID 34389713

Citations 15

Authors

Karin H Nilsson

Petra Henning

Maha El Shahawy

Maria Nethander

Thomas Levin Andersen

Charlotte Ejersted

Jianyao Wu

Karin L Gustafsson

Antti Koskela

Juha Tuukkanen

Pedro P C Souza

Jan Tuckermann

Mattias Lorentzon

Linda Engstrom Ruud

Terho Lehtimaki

Jon H Tobias

Sirui Zhou

Ulf H Lerner

J Brent Richards

Sofia Moverare-Skrtic

Claes Ohlsson

Affiliations

Soon will be listed here.

Abstract

With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.

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