Sp7 transcription factor

SP7
Identifiers
AliasesSP7, OI11, OI12, OSX, osterix, Sp7 transcription factor
External IDsMGI: 2153568 HomoloGene: 15607 GeneCards: SP7
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q13.13Start53,326,575 bp[1]
End53,345,315 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

121340

170574

Ensembl

ENSG00000170374

ENSMUSG00000060284

UniProt

Q8TDD2

Q8VI67

RefSeq (mRNA)

NM_001173467
NM_001300837
NM_152860

NM_130458
NM_001348205

RefSeq (protein)

NP_001287766.1
NP_001166938
NP_001287766
NP_690599

NP_569725
NP_001335134

Location (UCSC)Chr 12: 53.33 – 53.35 MbChr 15: 102.36 – 102.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transcription factor Sp7, also called Osterix (Osx), is a protein that in humans is encoded by the SP7 gene.[5] In mesenchymal precursor cells expressing Runx-2, Sp7 expression will induce these cells to differentiate into osteoblasts, and subsequently osteocytes during bone formation.[5] Sp7 also plays a dual role to inhibit chondrocyte differentiation.[6] Mutations of this gene are associated with Osteogenesis Imperfecta (OI), osteoporosis, and other bone diseases.[7]

Knockout model


Inactivation of Sp7 in adult mice led to lack of new bone formation, cartilage accumulation (specifically beneath the growth plate) and other defects in osteocyte maturation and function.[8] Ablation of Sp7 genes also led to decreased expression of various other osteocyte-specific markers such as: Sost, Dkk1, Dmp1, and Phe. Researchers also revealed the importance of Sp7 in the removal of the cartilaginous matrix and remodeling process with bone tissues.[8]

Clinical relevance

Bone fracture repair

Accelerated bone fracture healing was found when researchers implanted Sp7-expressing bone marrow stroma cells at a site of bone fracture. It was found that the mechanism by which Sp7-expression accelerated bone healing was by new bone formation as well as induction of neighboring cells to express bone-specific genes.[9] Similar results have been seen with osseo-integrating implants.[10][11]

Treatment of osteosarcomas

Sp7 expression is decreased in mouse and human osteosarcoma cell lines as compared to normal osteoblasts. Transfection of the SP7 gene into the mouse osteosarcoma cells reduced tumor incidence, tumor volume, and lung metastasis. Sp7 expression was also found to decrease bone destruction by the sarcoma.[12]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000170374 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000060284 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. 1 2 Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (January 2002). "The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation". Cell. 108 (1): 17–29. doi:10.1016/S0092-8674(01)00622-5. PMID 11792318.
  6. ↑ Kaback LA, Soung do Y, Naik A, Smith N, Schwarz EM, O'Keefe RJ, Drissi H (2008). "Osterix/Sp7 regulates mesenchymal stem cell mediated endochondral ossification". Journal of Cellular Physiology. 214 (1): 173–82. doi:10.1002/jcp.21176. PMID 17579353.
  7. ↑ Lapunzina P, Aglan M, Temtamy S, Caparrós-Martín JA, Valencia M, Letón R, Martínez-Glez V, Elhossini R, Amr K, Vilaboa N, Ruiz-Perez VL (2010). "Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta". American Journal of Human Genetics. 87 (1): 110–4. doi:10.1016/j.ajhg.2010.05.016. PMC 2896769. PMID 20579626.
  8. 1 2 Zhou X, Zhang Z, Feng JQ, Dusevich VM, Sinha K, Zhang H, Darnay BG, de Crombrugghe B (2010). "Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice". Proceedings of the National Academy of Sciences of the United States of America. 107 (29): 12919–24. doi:10.1073/pnas.0912855107. PMC 2919908. PMID 20615976.
  9. ↑ Tu Q, Valverde P, Li S, Zhang J, Yang P, Chen J (2007). "Osterix overexpression in mesenchymal stem cells stimulates healing of critical-sized defects in murine calvarial bone". Tissue Engineering. 13 (10): 2431–40. doi:10.1089/ten.2006.0406. PMC 2835465. PMID 17630878.
  10. ↑ Tu Q, Valverde P, Chen J (2006). "Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells". Biochemical and Biophysical Research Communications. 341 (4): 1257–65. doi:10.1016/j.bbrc.2006.01.092. PMC 2831616. PMID 16466699.
  11. ↑ Xu B, Zhang J, Brewer E, Tu Q, Yu L, Tang J, Krebsbach P, Wieland M, Chen J (2009). "Osterix enhances BMSC-associated osseointegration of implants". Journal of Dental Research. 88 (11): 1003–7. doi:10.1177/0022034509346928. PMC 2831612. PMID 19828887.
  12. ↑ Cao Y, Zhou Z, de Crombrugghe B, Nakashima K, Guan H, Duan X, Jia SF, Kleinerman ES (2005). "Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma". Cancer Research. 65 (4): 1124–8. doi:10.1158/0008-5472.CAN-04-2128. PMID 15734992.

Further reading

  • Gronthos S, Chen S, Wang CY, Robey PG, Shi S (April 2003). "Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin". Journal of Bone and Mineral Research. 18 (4): 716–22. doi:10.1359/jbmr.2003.18.4.716. PMID 12674332.
  • Milona MA, Gough JE, Edgar AJ (November 2003). "Expression of alternatively spliced isoforms of human Sp7 in osteoblast-like cells". BMC Genomics. 4 (1): 43. doi:10.1186/1471-2164-4-43. PMC 280673. PMID 14604442.
  • Gao Y, Jheon A, Nourkeyhani H, Kobayashi H, Ganss B (October 2004). "Molecular cloning, structure, expression, and chromosomal localization of the human Osterix (SP7) gene". Gene. 341: 101–10. doi:10.1016/j.gene.2004.05.026. PMID 15474293.
  • Morsczeck C (February 2006). "Gene expression of runx2, Osterix, c-fos, DLX-3, DLX-5, and MSX-2 in dental follicle cells during osteogenic differentiation in vitro". Calcified Tissue International. 78 (2): 98–102. doi:10.1007/s00223-005-0146-0. PMID 16467978.
  • Wu L, Wu Y, Lin Y, Jing W, Nie X, Qiao J, Liu L, Tang W, Tian W (July 2007). "Osteogenic differentiation of adipose derived stem cells promoted by overexpression of osterix". Molecular and Cellular Biochemistry. 301 (1–2): 83–92. doi:10.1007/s11010-006-9399-9. PMID 17206379.
  • Amorim BR, Okamura H, Yoshida K, Qiu L, Morimoto H, Haneji T (April 2007). "The transcriptional factor Osterix directly interacts with RNA helicase A". Biochemical and Biophysical Research Communications. 355 (2): 347–51. doi:10.1016/j.bbrc.2007.01.150. PMID 17303075.
  • Fan D, Chen Z, Wang D, Guo Z, Qiang Q, Shang Y (June 2007). "Osterix is a key target for mechanical signals in human thoracic ligament flavum cells". Journal of Cellular Physiology. 211 (3): 577–84. doi:10.1002/jcp.21016. PMID 17311298.
  • Zheng L, Iohara K, Ishikawa M, Into T, Takano-Yamamoto T, Matsushita K, Nakashima M (July 2007). "Runx3 negatively regulates Osterix expression in dental pulp cells". The Biochemical Journal. 405 (1): 69–75. doi:10.1042/BJ20070104. PMC 1925241. PMID 17352693.
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