Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin.
| Title: | Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin. |
|---|---|
| Authors: | Wang JS; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Kamath T; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Mazur CM; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Mirzamohammadi F; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Department of Plastic and Reconstructive Surgery, Wright State University, Dayton, OH, USA.; Rotter D; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; University of Applied Sciences Technikum Wien, Vienna, Austria.; Hojo H; 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.; Castro CD; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Tokavanich N; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Patel R; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Govea N; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Department of Anesthesiology, Weill Cornell Medical School, New York, NY, USA.; Enishi T; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Department of Orthopedic Surgery, Tokushima Municipal Hospital, Tokushima, Japan.; Wu Y; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.; da Silva Martins J; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Bruce M; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Brooks DJ; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MaA, USA.; Bouxsein ML; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MaA, USA.; Tokarz D; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Department of Chemistry, Saint Mary's University, Halifax, Canada.; Lin CP; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Abdul A; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Macosko EZ; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Fiscaletti M; Pediatric Department, Sainte-Justine University Hospital Centre, Montreal, Canada.; Munns CF; Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, NSW, Australia.; Discipline of Paediatrics & Child Health, University of Sydney, Sydney, 2006, Australia.; Ryder P; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Broad Institute of Harvard and MIT, Imaging Platform, Cambridge, MA, USA.; Kost-Alimova M; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Broad Institute of Harvard and MIT, Center for the Development of Therapeutics, Cambridge, MA, USA.; Byrne P; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Broad Institute of Harvard and MIT, Center for the Development of Therapeutics, Cambridge, MA, USA.; Cimini B; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Broad Institute of Harvard and MIT, Imaging Platform, Cambridge, MA, USA.; Fujiwara M; Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.; Kronenberg HM; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Wein MN; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. mnwein@mgh.harvard.edu.; Broad Institute of Harvard and MIT, Cambridge, MA, USA. mnwein@mgh.harvard.edu.; Harvard Stem Cell Institute, Cambridge, MA, USA. mnwein@mgh.harvard.edu. |
| Source: | Nature communications [Nat Commun] 2021 Nov 01; Vol. 12 (1), pp. 6271. Date of Electronic Publication: 2021 Nov 01. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Bone Diseases/*metabolism ; Dendrites/*metabolism ; Muscle Proteins/*metabolism ; Osteocytes/*metabolism ; Sp7 Transcription Factor/*metabolism ; Transcription Factors/*metabolism; Bone Diseases/genetics ; Bone Diseases/physiopathology ; Muscle Proteins/genetics ; Sp7 Transcription Factor/genetics ; Transcription Factors/genetics ; Adolescent ; Animals ; Female ; Gene Expression Regulation ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation |
| 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.; (© 2021. The Author(s).) |
| References: | Sci Rep. 2018 Jun 25;8(1):9588. (PMID: 29942049); Cell. 2019 Jun 13;177(7):1873-1887.e17. (PMID: 31178122); Bone. 2008 Mar;42(3):524-34. (PMID: 18178537); Bioinformatics. 2015 Jan 15;31(2):166-9. (PMID: 25260700); J Bone Miner Res. 2000 Jan;15(1):60-7. (PMID: 10646115); Nat Protoc. 2016 Sep;11(9):1757-74. (PMID: 27560178); Bone. 2015 Jun;75:144-50. (PMID: 25708054); Nature. 2003 May 15;423(6937):337-42. (PMID: 12748652); Development. 2017 Jan 15;144(2):334-344. (PMID: 27993976); Genesis. 2013 Apr;51(4):246-58. (PMID: 23180553); Nat Genet. 2012 Apr 15;44(5):491-501. (PMID: 22504420); Nat Genet. 2009 Nov;41(11):1199-206. (PMID: 19801982); J Bone Miner Res. 2012 Feb;27(2):360-73. (PMID: 22161640); PLoS Comput Biol. 2015 Apr 17;11(4):e1004219. (PMID: 25885710); Nucleic Acids Res. 2014 Dec 16;42(22):e168. (PMID: 25300484); Nature. 2018 Aug;560(7719):494-498. (PMID: 30089906); Biochem Biophys Res Commun. 2016 Sep 9;478(1):110-115. (PMID: 27449610); Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5. (PMID: 27079975); Genome Biol. 2009;10(3):R25. (PMID: 19261174); Bone. 2016 Aug;89:7-15. (PMID: 27085457); Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):16042-7. (PMID: 26668395); Nature. 2019 May;569(7755):222-228. (PMID: 30971824); Cell. 2018 Aug 9;174(4):1015-1030.e16. (PMID: 30096299); Bone. 2018 May;110:66-75. (PMID: 29382611); Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16689-94. (PMID: 15539460); Endocr Rev. 2013 Oct;34(5):658-90. (PMID: 23612223); Biochemistry. 2009 Mar 10;48(9):1975-83. (PMID: 19215067); Nature. 2005 Jun 16;435(7044):969-73. (PMID: 15959517); Elife. 2020 Apr 14;9:. (PMID: 32286228); Gigascience. 2017 Dec 1;6(12):1-5. (PMID: 28327978); Bone. 2009 Oct;45(4):682-92. (PMID: 19539797); Nucleic Acids Res. 2010 Sep;38(17):e169. (PMID: 20660011); OMICS. 2012 May;16(5):284-7. (PMID: 22455463); Arthritis Res Ther. 2008;10(1):201. (PMID: 18226189); Clin Epigenetics. 2016 Nov 21;8:123. (PMID: 27895807); EMBO J. 2003 Dec 1;22(23):6267-76. (PMID: 14633986); Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):14092-7. (PMID: 22886088); Biotechniques. 2012 Jun;52(6):361-73. (PMID: 22668415); Bone. 2016 Apr;85:91-8. (PMID: 26851122); Science. 2000 Sep 1;289(5484):1501-4. (PMID: 10968779); Gene Expr Patterns. 2012 Aug-Sep;12(7-8):228-35. (PMID: 22575304); Dev Cell. 2016 May 9;37(3):238-53. (PMID: 27134141); Development. 2019 Jul 16;146(14):. (PMID: 31311805); Am J Med Genet A. 2019 Dec;179(12):2393-2419. (PMID: 31633310); Nat Neurosci. 2011 Mar;14(3):285-93. (PMID: 21346746); Bioinformatics. 2011 Jun 15;27(12):1653-9. (PMID: 21543442); Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14665-70. (PMID: 16203988); Nat Commun. 2021 May 5;12(1):2444. (PMID: 33953184); Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7296-7304. (PMID: 32170021); Mol Cell Biol. 2006 Jun;26(12):4539-52. (PMID: 16738320); Dev Dyn. 2006 Jan;235(1):176-90. (PMID: 16258960); Annu Rev Cell Dev Biol. 2009;25:629-48. (PMID: 19575648); J Bone Miner Res. 2007 Dec;22(12):1957-67. (PMID: 17696759); Nature. 2016 Nov 09;539(7628):242-247. (PMID: 27830782); FASEB J. 2005 Nov;19(13):1842-4. (PMID: 16123173); J Bone Miner Res. 2020 May;35(5):966-977. (PMID: 31910292); Annu Rev Physiol. 2020 Feb 10;82:485-506. (PMID: 32040934); Science. 1999 Oct 22;286(5440):785-90. (PMID: 10531066); PLoS Biol. 2018 Jul 3;16(7):e2005970. (PMID: 29969450); Bone. 2019 May;122:101-113. (PMID: 30743014); Genome Res. 2003 Nov;13(11):2498-504. (PMID: 14597658); Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12919-24. (PMID: 20615976); Sci Rep. 2017 Mar 22;7:44618. (PMID: 28327602); J Bone Miner Res. 2006 Apr;21(4):605-15. (PMID: 16598381); Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308); Genes Dev. 2012 Dec 15;26(24):2802-16. (PMID: 23249739); J Bone Miner Res. 2011 Feb;26(2):229-38. (PMID: 21254230); Bone. 2011 Oct;49(4):683-92. (PMID: 21820092); Cell. 2019 Jun 13;177(7):1915-1932.e16. (PMID: 31130381); Genome Biol. 2008;9(9):R137. (PMID: 18798982); Bioinformatics. 2015 Jul 15;31(14):2382-3. (PMID: 25765347); Cell Metab. 2019 Mar 5;29(3):627-637.e5. (PMID: 30661929); J Bone Miner Res. 2015 Mar;30(3):400-11. (PMID: 25271055); Nat Commun. 2016 Oct 19;7:13176. (PMID: 27759007); J Biol Chem. 2004 May 7;279(19):19391-5. (PMID: 15044443); PLoS One. 2017 Oct 24;12(10):e0186846. (PMID: 29065178); Curr Osteoporos Rep. 2019 Dec;17(6):548-559. (PMID: 31741222); J Clin Invest. 2017 Nov 1;127(11):4136-4147. (PMID: 28990933); Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886); Nat Rev Endocrinol. 2016 Oct;12(10):593-605. (PMID: 27230951); Cell. 2002 Jan 11;108(1):17-29. (PMID: 11792318); Dev Biol. 2013 Feb 1;374(1):234-44. (PMID: 23201014); Nat Biotechnol. 2014 Apr;32(4):381-386. (PMID: 24658644); Nat Biotechnol. 2010 May;28(5):495-501. (PMID: 20436461); Mol Endocrinol. 2014 Jul;28(7):1150-65. (PMID: 24877565); Curr Osteoporos Rep. 2017 Oct;15(5):401-411. (PMID: 28891009); J Dent Res. 2007 Apr;86(4):320-5. (PMID: 17384025); J Biol Chem. 2007 Dec 14;282(50):36454-62. (PMID: 17951249); Mol Biol Cell. 2021 Apr 19;32(9):995-1005. (PMID: 33534641); Nat Commun. 2020 Jul 1;11(1):3282. (PMID: 32612176); Nat Commun. 2019 Apr 3;10(1):1523. (PMID: 30944313); J Biol Chem. 2003 Dec 12;278(50):50563-71. (PMID: 14523025); Dev Cell. 2007 Mar;12(3):377-89. (PMID: 17336904); Biochem Biophys Res Commun. 2011 Apr 22;407(4):842-7. (PMID: 21463606); Methods Mol Biol. 2012;816:55-66. (PMID: 22130922); Dev Biol. 2013 Nov 1;383(1):90-105. (PMID: 23994639); J Mol Diagn. 2012 Jan;14(1):22-9. (PMID: 22166544); J Bone Miner Metab. 2007;25(6):400-6. (PMID: 17968492); J Bone Miner Res. 2009 Apr;24(4):597-605. (PMID: 19049324); Bioinformatics. 2010 Mar 15;26(6):841-2. (PMID: 20110278); Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13648-53. (PMID: 20643964); Am J Hum Genet. 2010 Jul 9;87(1):110-4. (PMID: 20579626); Cell Rep. 2021 Jul 13;36(2):109380. (PMID: 34260913); Nat Rev Neurosci. 2007 May;8(5):331-40. (PMID: 17453014); EMBO J. 2010 Jan 6;29(1):68-79. (PMID: 19927124); J Bone Miner Res. 2016 Nov;31(11):2001-2007. (PMID: 27237054); J Histochem Cytochem. 2005 Oct;53(10):1181-7. (PMID: 15923362); Circ Res. 2018 Mar 2;122(5):742-751. (PMID: 29326144); Cell Rep. 2019 Jul 9;28(2):302-311.e5. (PMID: 31291568); Curr Osteoporos Rep. 2018 Dec;16(6):746-753. (PMID: 30406580) |
| Grant Information: | P30 DK043351 United States DK NIDDK NIH HHS; P30 AR066261 United States AR NIAMS NIH HHS; S10 OD021577 United States OD NIH HHS; T32 DK007028 United States DK NIDDK NIH HHS; T32 GM008313 United States GM NIGMS NIH HHS; K08 AR067285 United States AR NIAMS NIH HHS |
| Substance Nomenclature: | 0 (Muscle Proteins); 0 (OSTN protein, human); 0 (Ostn protein, mouse); 0 (Sp7 Transcription Factor); 0 (SP7 protein, human); 0 (Sp7 protein, mouse); 0 (Transcription Factors) |
| Entry Date(s): | Date Created: 20211102 Date Completed: 20211224 Latest Revision: 20241019 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8560803 |
| DOI: | 10.1038/s41467-021-26571-7 |
| PMID: | 34725346 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't