Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Yang, Tao; Zheng, Xiaofei; Li, Mei; Lin, Xi; Yin, Qian

doi:10.7314/apjcp.2013.14.9.5379

Cited by 14 publications

(14 citation statements)

References 21 publications

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“…Histological analysis of H&E and TRAP staining revealed that the patient-derived GCTB cells survived, and caused an osteolytic reaction in the bone environment. Furthermore, previous studies have reported that stromal cells can differentiate into mature osteoblasts, adipocytes and chondrocytes (11,12,(33)(34)(35)(36). Observed differences between the results of the present study and others may indicate that stromal cells undergo multidirectional differentiation, which may be influenced by the tissue microenvironment.…”

Section: Discussioncontrasting

confidence: 86%

Intratibial injection of patient‑derived tumor cells from giant cell tumor of bone elicits osteolytic reaction in nude mouse

Zhou

et al. 2018

Oncol Lett

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There have been various reports in the literature of an model for giant cell tumor of bone (GCTB). However, few suitable animal models of GCTB have been established, due to the fact that GCTB contains three histologically different cell types. To the best of our knowledge, injection of patient-derived GCTB cells into bone environment has not been reported until now. In the present study, the biological behavior of GCTB cells in nude mice was investigated through intratibial injection of patient-derived GCTB cells. Patient-derived GCTB cells were obtained from 5 patients who had not undergone chemo- and radiotherapy. Once isolated, the cell suspension was injected into the tibias of nude mice. The growth process was monitored by weekly observation and photographic documentation using X-ray. Four months after injection, nude mice were sacrificed and the injected tibial samples were fixed, and further analyzed using micro-computed tomography (micro-CT), standard histology, tartrate-resistant acid phosphatase (TRAP) staining and mitochondrial immunofluorescence staining. X-ray, micro-CT and standard histology revealed osteolytic destruction in the proximal end of the tibia. TRAP staining identified TRAP-positive, osteoclast-like cells distributed in the bone marrow interface of the lesion area. Anti-human mitochondrial immunofluorescence staining confirmed that the surviving cells in the osteolytic destruction were of human GCTB cell origin. These findings indicate that intratibial injection of patient-derived GCTB cells may elicit osteolytic destruction in nude mice. The results of the current study present a novel animal model for GCTB, opening new perspectives to investigate this disease and develop therapeutic agents.

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Section: Discussioncontrasting

confidence: 86%

Intratibial injection of patient‑derived tumor cells from giant cell tumor of bone elicits osteolytic reaction in nude mouse

Zhou

et al. 2018

Oncol Lett

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“…We suggest that systemic chemotherapy be considered if local control fails following radiotherapy or distal metastases are identified. Studies have indicated that topical or systemic use of bisphosphonates may present a novel adjuvant therapy for GCT by inducing apoptosis of stromal tumor cells and stimulating osteogenic differentiation of the remaining tumor stromal cells following surgery ( 20 – 22 ).…”

Section: Discussionmentioning

confidence: 99%

Giant cell tumor of the clivus: A case report and review of the literature

Zhao¹,

Tao²,

Zhi³

et al. 2014

Oncology Letters

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Giant cell tumors (GCTs) mainly occur in metaphyses of long bones and are generally considered histologically benign; however, GCTs may be locally aggressive with a high rate of local recurrence and exhibit the potential for distant metastasis. Primary GCT of the clivus is extremely rare and is easily misdiagnosed and, thus, treatment remains controversial. The present report describes the case of a 22-year-old male with GCT located in the skull base originating from the clivus, with the involvement of multiple cranial nerves, which was successfully treated with transnasal transsphenoidal surgery following adjuvant radiotherapy and intravenous bisphosphonate administration. The patient remains symptom free at two years of follow-up. This report contributes to the limited literature regarding GCTs of the skull.

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“… 1-4 BPs are currently administered as anti-resorptive medications to manage hypercalcemia of malignancy, skeletal-related events accompanying bone metastases in the context of solid tumors, lytic lesions in multiple myeloma, Paget’s disease of the bone, osteogenesis imperfecta, osteoporosis, and osteopenia. 5-12 BPs have high affinity for sites of active bone remodeling, where they suppress, both directly and indirectly, osteoclast-mediated bone resorption. 13-15 The inhibitory effects of BPs on the boneresorbing activity and on the development, proliferation and viability of macrophage lineage cells have been also reported.…”

Section: Introductionmentioning

confidence: 99%

RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects

et al. 2015

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Osteonecrosis of the jaw (ONJ) is a chronic complication affecting long-term bisphosphonate-treated subjects, recognized by non-healing exposed bone in the maxillofacial region. The pathophysiological mechanism underlying ONJ has not been fully elucidated. The aim of the present study was to investigate the role of RANK/RANKL/OPG signaling pathway and, in parallel, to evaluate angiogenic and matrix mineralization processes in jaw bone necrotic samples obtained from bisphosphonate-treated subjects with established ONJ. Necrotic bone samples and native bone samples were processed for Light and Field Emission in Lens Scanning Electron Microscope (FEISEM) analyses, for Real-Time RT-PCR to evaluate the gene expression of TNFRSF11A (RANK), TNFSF11 (RANKL), and TNFSF11B (OPG) and for immunohistochemical analyses of VEGF and BSP expression. Morphological analyses performed by Light microscope and FEISEM show empty osteocytic lacunae and alteration of lamellar organization with degradation of the mineralized bone matrix in necrotic bone samples. A significant increase in TNFRSF11A, TNFSF11, TRAF6 and NFAT2 gene expression, and a reduction of TNFSF11B gene transcription level compared is also showed in necrotic bone compared to control samples. No significant difference of VEGF expression is evidenced, while lower BSP expression in necrotic bone compared to healthy samples is found. Even if the pathogenesis of bisphosphonate-associated ONJ remains unknown, a link between oral pathogens and its development seems to exist. We suppose lipopolysaccharide produced by bacteria colonizing and infecting necrotic bone and the surrounding viable area could trigger RANK/RANKL/OPG signaling pathway and, in this context, osteoclasts activation could be considered as a protective strategy carried out by the host bone tissue to delimitate the necrotic area and to counteract infection.

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Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Cited by 14 publications

References 21 publications

Intratibial injection of patient‑derived tumor cells from giant cell tumor of bone elicits osteolytic reaction in nude mouse

Intratibial injection of patient‑derived tumor cells from giant cell tumor of bone elicits osteolytic reaction in nude mouse

Giant cell tumor of the clivus: A case report and review of the literature

RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects

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