Title

Osteoclast inhibition impairs chondrosarcoma growth and bone destruction

UMMS Affiliation

Department of Cell and Developmental Biology

Date

12-1-2014

Document Type

Article

Subjects

Animals; Bone Resorption; Bone and Bones; Chondrosarcoma; Diphosphonates; Imidazoles; Male; Osteoclasts; Parathyroid Hormone-Related Protein; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta2

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.

Rights and Permissions

Citation: 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.

Related Resources

Link to Article in PubMed

Keywords

chondrosarcoma, osteoclast, bisphosphonate, osteolysis

Journal Title

Journal of orthopaedic research : official publication of the Orthopaedic Research Society