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Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin.
Wang, Jialiang S; Kamath, Tushar; Mazur, Courtney M; Mirzamohammadi, Fatemeh; Rotter, Daniel; Hojo, Hironori; Castro, Christian D; Tokavanich, Nicha; Patel, Rushi; Govea, Nicolas; Enishi, Tetsuya; Wu, Yunshu; da Silva Martins, Janaina; Bruce, Michael; Brooks, Daniel J; Bouxsein, Mary L; Tokarz, Danielle; Lin, Charles P; Abdul, Abdul; Macosko, Evan Z; Fiscaletti, Melissa; Munns, Craig F; Ryder, Pearl; Kost-Alimova, Maria; Byrne, Patrick; Cimini, Beth; Fujiwara, Makoto; Kronenberg, Henry M; Wein, Marc N.
Afiliação
  • Wang JS; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Kamath T; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Mazur CM; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Mirzamohammadi F; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Rotter D; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Hojo H; Department of Plastic and Reconstructive Surgery, Wright State University, Dayton, OH, USA.
  • Castro CD; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Tokavanich N; University of Applied Sciences Technikum Wien, Vienna, Austria.
  • Patel R; Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
  • Govea N; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Enishi T; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Wu Y; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • da Silva Martins J; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Bruce M; Department of Anesthesiology, Weill Cornell Medical School, New York, NY, USA.
  • Brooks DJ; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Bouxsein ML; Department of Orthopedic Surgery, Tokushima Municipal Hospital, Tokushima, Japan.
  • Tokarz D; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Lin CP; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Abdul A; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Macosko EZ; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Fiscaletti M; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Munns CF; Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MaA, USA.
  • Ryder P; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Kost-Alimova M; Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MaA, USA.
  • Byrne P; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Cimini B; Department of Chemistry, Saint Mary's University, Halifax, Canada.
  • Fujiwara M; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Kronenberg HM; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Wein MN; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteócitos / Fatores de Transcrição / Doenças Ósseas / Dendritos / Fator de Transcrição Sp7 / Proteínas Musculares Limite: Adolescent / Animals / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteócitos / Fatores de Transcrição / Doenças Ósseas / Dendritos / Fator de Transcrição Sp7 / Proteínas Musculares Limite: Adolescent / Animals / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article