AIMS: To assess the immunophenotypic and mRNA expression of sclerostin in human skeletal tissues and in a wide range of benign and malignant bone tumours and tumour-like lesions. METHODS AND RESULTS: Sclerostin expression was evaluated by immunohistochemistry and quantitative polymerase chain reaction (PCR). In lamellar and woven bone, there was strong sclerostin expression by osteocytes. Osteoblasts and other cell types in bone were negative. Hypertrophic chondrocytes in the growth plate and mineralized cartilage cells in zone 4 of hyaline articular cartilage strongly expressed sclerostin, but most chondrocytes in hyaline cartilage were negative. In primary bone-forming tumours, including osteosarcomas, there was patchy expression of sclerostin in mineralized osteoid and bone. Sclerostin staining was seen in woven bone in fibrous dysplasia, in osteofibrous dysplasia, and in reactive bone formed in fracture callus, in myositis ossificans, and in the wall of solitary bone cysts and aneurysmal bone cysts. Sclerostin was expressed by hypertrophic chondrocytes in osteochondroma and chondroblasts in chondroblastoma, but not by tumour cells in other bone tumours, including myeloma and metastatic carcinoma. mRNA expression of sclerostin was identified by quantitative PCR in osteosarcoma specimens and cell lines. CONCLUSIONS: Sclerostin is an osteocyte marker that is strongly expressed in human woven and lamellar bone and mineralizing chondrocytes. This makes it a useful marker with which to identify benign and malignant osteogenic tumours and mineralizing cartilage tumours, such as chondroblastomas and other lesions in which there is bone formation.
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bone, osteocyte, osteosarcoma, sclerostin, tumour, Biomarkers, Tumor, Bone Morphogenetic Proteins, Bone Neoplasms, Bone and Bones, Genetic Markers, Humans, Immunohistochemistry, Osteocytes, Osteogenesis, Real-Time Polymerase Chain Reaction