Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin.
Nat Commun
; 12(1): 6271, 2021 11 01.
Article
em En
| MEDLINE
| ID: mdl-34725346
ABSTRACT
Some osteoblasts embed within bone matrix, change shape, and become dendrite-bearing osteocytes. The circuitry that drives dendrite formation during "osteocytogenesis" is poorly understood. Here we show that deletion of Sp7 in osteoblasts and osteocytes causes defects in osteocyte dendrites. Profiling of Sp7 target genes and binding sites reveals unexpected repurposing of this transcription factor to drive dendrite formation. Osteocrin is a Sp7 target gene that promotes osteocyte dendrite formation and rescues defects in Sp7-deficient mice. Single-cell RNA-sequencing demonstrates defects in osteocyte maturation in the absence of Sp7. Sp7-dependent osteocyte gene networks are associated with human skeletal diseases. Moreover, humans with a SP7R316C mutation show defective osteocyte morphology. Sp7-dependent genes that mark osteocytes are enriched in neurons, highlighting shared features between osteocytic and neuronal connectivity. These findings reveal a role for Sp7 and its target gene Osteocrin in osteocytogenesis, revealing that pathways that control osteocyte development influence human bone diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteócitos
/
Fatores de Transcrição
/
Doenças Ósseas
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Dendritos
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Fator de Transcrição Sp7
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Proteínas Musculares
Limite:
Adolescent
/
Animals
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Female
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Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2021
Tipo de documento:
Article