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Osteocytes Serve as a Progenitor Cell of Osteosarcoma
Author(s) -
Sottnik Joseph L.,
Campbell Brittany,
Mehra Rohit,
BehbahaniNejad Omid,
Hall Christopher L.,
Keller Evan T.
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24793
Subject(s) - dmp1 , osteocyte , progenitor cell , cementoblast , osteosarcoma , progenitor , cancer research , pathology , cell culture , microbiology and biotechnology , osteoblast , medicine , chemistry , biology , stem cell , immunology , viral matrix protein , dentin , in vitro , biochemistry , virus , cementum , genetics
Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO‐Y4, a SV‐40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO‐Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. J. Cell. Biochem. 115: 1420–1429, 2014. © 2014 Wiley Periodicals, Inc.