A patient with femoral osteitis fibrosa cystica mimicking bone neoplasm: a case report.

BACKGROUND: Osteitis fibrosa cystica is a rare, benign and osteolytic lesion attributed to hyperparathyroidism. The high level of parathyroid hormone cause rapid bone loss. CASE PRESENTATION: The patient is a 50-year-old male complaining of severe and persistent pain in the right knee joint. Imaging studies were suspicious for a benign tumor in the right distal femur. Biopsy under CT guidance showed numerous osteoclast aggregation and hemosiderin deposition around the bone trabeculae. Blood tests disclosed significantly elevated parathyroid hormone, serum calcium, serum alkaline phosphatase. Parathyroid ultrasonography and CT scan showed a solid mass in front of the trachea at the thoracic entrance plane. After resection of the mass, the clinical symptoms were relieved and the radiological results were significantly improved, which further confirmed the diagnosis. CONCLUSIONS: Metabolic diseases-associated bone lesions require a comprehensive diagnosis of multiple inspection items. An interprofessional team approach to the diagnosis and treatment of osteitis fibrosa cystica will provide the best outcome.

CCAR2 promotes a malignant phenotype of osteosarcoma through Wnt/ß-catenin-dependent transcriptional activation of SPARC.

CCAR2 plays a pivotal role in the regulation of the DNA damage response and cancer progression. Although aberrant expression of CCAR2 has been reported in several types of cancer, its biological function and molecular mechanism in osteosarcoma (OS) have not yet been fully elucidated. Here, we show that silence of CCAR2 prevented the malignant phenotype of OS cell in vitro and decreased tumor growth in nude mice. By analyzing the transcriptomic profile of CCAR2 knockdown U2OS cells, we identified secreted protein acidic and rich in cysteine (SPARC) is tightly regulated by CCAR2. Mechanically, we found that SPARC is transcriptionally regulated by Wnt/ß-catenin signaling, and CCAR2 acts as a co-activator of Wnt/ß-catenin signaling to regulate the expression of SPARC in OS cells. Additionally, SPARC knockdown largely eliminated the malignant phenotype induced by CCAR2 overexpression and forced expression of SPARC promoted the malignant phenotype of CCAR2-depleted cells. In conclusion, our results suggest that CCAR2 exerted oncogenic roles in OS cells mainly via up-regulating SPARC expression and targeting the CCAR2-SPARC axis might have promising application prospect for the treatment of osteosarcoma.

SUMO-specific protease 2 (SENP2) functions as a tumor suppressor in osteosarcoma via SOX9 degradation.

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, the pathogenesis of which remain largely unknown. Small ubiquitin-like modifier (SUMO)-Specific Protease 2 (SENP2) has been reported to serve as a tumor suppressor in hepatocellular carcinoma cells. The aim of the present study was to investigate the critical role of SENP2 in OS cells. Using reverse transcription-quantitative polymerase chain reaction and western blot assays, it was observed that SENP2 was significantly downregulated in clinical OS tissues compared with adjacent normal samples. Ectopic expression of SENP2 resulted in the suppression of proliferation, migration and invasion in OS cells, whereas SENP2 knockdown by CRISPR-Cas9-based gene editing had the opposite effect. SENP2 is associated with the proteasome-dependent ubiquitination and degradation of SRY-box-9 (SOX9). SOX9 silencing impaired SENP2-depletion-induced accelerated cell growth and migration. Together, these results suggest that SOX9 is a critical downstream effector of the tumor suppressor SENP2 in OS.