RSPO3 is important for trabecular bone and fracture risk in mice and humans.
Nat Commun
; 12(1): 4923, 2021 08 13.
Article
en En
| MEDLINE
| ID: mdl-34389713
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trombospondinas
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Predisposición Genética a la Enfermedad
/
Polimorfismo de Nucleótido Simple
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Fracturas Óseas
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Hueso Esponjoso
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article