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    Osteoclast inhibition impairs chondrosarcoma growth and bone destruction

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    Authors
    Otero, Jesse E.
    Stevens, Jeff W.
    Malandra, Allison E.
    Fredericks, Douglas C.
    Odgren, Paul R.
    Buckwalter, Joseph A.
    Morcuende, Jose
    UMass Chan Affiliations
    Department of Cell and Developmental Biology
    Document Type
    Journal Article
    Publication Date
    2014-12-01
    Keywords
    Animals
    Bone Resorption
    Bone and Bones
    Chondrosarcoma
    Diphosphonates
    Imidazoles
    Male
    Osteoclasts
    Parathyroid Hormone-Related Protein
    Rats
    Rats, Sprague-Dawley
    Transforming Growth Factor beta2
    chondrosarcoma
    osteoclast
    bisphosphonate
    osteolysis
    Cell and Developmental Biology
    Cell Biology
    Neoplasms
    Orthopedics
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    Link to Full Text
    http://dx.doi.org/10.1002/jor.22714
    Abstract
    Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients.
    Source
    J Orthop Res. 2014 Dec;32(12):1562-71. doi: 10.1002/jor.22714. Epub 2014 Aug 13. Link to article on publisher's site.
    DOI
    10.1002/jor.22714
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/26458
    PubMed ID
    25125336
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/jor.22714
    Scopus Count
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