Transcription factor Sp7, also called Osterix (Osx), is a protein that in humans is encoded by the SP7gene.[1] In mesenchymal precursor cells expressing Runx-2, Sp7 expression will induce these cells to differentiate into osteoblasts, and subsequently osteocytes during bone formation.[1] Sp7 also plays a dual role to inhibit chondrocyte differentiation.[2] Mutations of this gene are associated with Osteogenesis Imperfecta (OI), osteoporosis, and other bone diseases.[3]
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.[4] 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.[4]
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.[5] Similar results have been seen with osseo-integrating implants.[6][7]
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.[8]
References
↑ 1.01.1Nakashima 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. PMID11792318.
↑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. PMID17579353.
↑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. PMID15734992.
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. PMID12674332.
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. PMID15474293.
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. PMID16467978.
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. PMID17206379.
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. PMID17303075.
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. PMID17311298.
