RSPO3 is important for trabecular bone and fracture risk in mice and humans

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 Engström Ruud, Terho Lehtimäki, Jon H. Tobias, Sirui Zhou, Ulf H. Lerner, J. Brent Richards, Sofia Movérare-Skrtic () and Claes Ohlsson ()
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Karin H. Nilsson: Sahlgrenska Academy at University of Gothenburg
Petra Henning: Sahlgrenska Academy at University of Gothenburg
Maha El Shahawy: Sahlgrenska Academy at University of Gothenburg
Maria Nethander: Sahlgrenska Academy at University of Gothenburg
Thomas Levin Andersen: University of Southern Denmark
Charlotte Ejersted: Odense University Hospital
Jianyao Wu: Sahlgrenska Academy at University of Gothenburg
Karin L. Gustafsson: Sahlgrenska Academy at University of Gothenburg
Antti Koskela: University of Oulu
Juha Tuukkanen: University of Oulu
Pedro P. C. Souza: Federal University of Goiás
Jan Tuckermann: University of Ulm
Mattias Lorentzon: Sahlgrenska Academy at University of Gothenburg
Linda Engström Ruud: Sahlgrenska Academy at the University of Gothenburg
Terho Lehtimäki: Fimlab Laboratories
Jon H. Tobias: University of Bristol
Sirui Zhou: McGill University
Ulf H. Lerner: Sahlgrenska Academy at University of Gothenburg
J. Brent Richards: McGill University
Sofia Movérare-Skrtic: Sahlgrenska Academy at University of Gothenburg
Claes Ohlsson: Sahlgrenska Academy at University of Gothenburg

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25124-2

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DOI: 10.1038/s41467-021-25124-2

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