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Expression of osteocalcin and its transcriptional regulators core‐binding factor alpha 1 and MSX2 in osteoid‐forming tumours
Author(s) -
Hopyan Sevan,
Gokgoz Nalan,
Bell Robert Stuart,
Andrulis Irene Louise,
Alman Benjamin Aaron,
Wunder Jay Steven
Publication year - 1999
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100170503
Subject(s) - osteocalcin , core binding factor , transcription factor , myositis ossificans , osteosarcoma , osteoblast , osteoid , biology , ossification , ctcf , medicine , endocrinology , cancer research , microbiology and biotechnology , pathology , anatomy , genetics , gene , alkaline phosphatase , biochemistry , enhancer , in vitro , enzyme
Osteosarcoma, fibrous dysplasia, and myositis ossificans contain osteoid‐producing cells that are not necessarily morphologically typical osteoblasts. Nevertheless, these pathologic cells may share differentiation steps with osteoblasts at the molecular level. Osteocalcin, a bone‐specific extracellular matrix protein, is a marker of mature osteoblasts. Osteocalcin is upregulated by the transcription factor core‐binding factor alpha 1, which is responsible for commitment to the osteoblastic lineage, and is downregulated by MSX2, a homeobox‐containing transcription factor expressed during the early proliferative phase of osteoblast differentiation. Semiquantitative reverse transcription‐polymerase chain reaction was used to compare expression levels of osteocalcin, core‐binding factor alpha 1 , and MSX2 in 34 osteosarcoma, five fibrous dysplasia, and five myositis ossificans specimens, as well as in seven normal cortical bone samples. Despite normal or elevated levels of core‐binding factor alpha‐1 expression in most specimens, osteocalcin expression was low or undetectable in most cases of osteosarcoma (25 of 34) and myositis ossificans (4 of 5). Single‐strand conformation polymorphism and sequencing did not identify and mutations in the DNA‐binding domain of core‐binding factor alpha 1 . However, a high level of MSX2 expression was demonstrated in these lesions, which may inhibit osteocalcin transcription. The presence of moderate levels of osteocalcin in fibrous dysplasia may contribute to the characteristic disconnected appearance of trabeculae in that entity because osteocalcin is a negative regulator of bone formation.