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Localized, tumor‐associated osteolysis involves the recruitment and activation of osteoclasts
Author(s) -
Clohisy Denis R.,
Ogilvie Christian M.,
Carpenter Randall J.,
Ramnaraine Margaret L. R.
Publication year - 1996
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100140103
Subject(s) - osteolysis , osteoclast , bone resorption , sarcoma , medicine , pathology , intramedullary rod , cancer research , anatomy , radiology , receptor
The cellular and biochemical mechanisms that direct destruction of bone at the site of tumor osteolysis are unknown. In order to understand this process better, a murine model designed for the study of tumor osteolysis was developed and the influence of osteolytic and nonosteolytic tumors on bone was investigated. Tumors developed following femoral intramedullary injection of sarcoma (2472) and melanoma (G3.26) cell lines: however, only tumors from the 2472 cell line caused osteolysis. It was determined that 2472 tumor‐induced osteolysis commenced 6 days after the femora had been inoculated with 2472 cells. There were more osteoclasts per millimeter of bone surface in 2472 tumor‐bearing limbs (16.7 ± 5.0) than in sham‐injected limbs (3.8 ± 0.9) (p < 0.015). In addition, an increase in the osteoclast size (area) was detected in 2472 tumor‐bearing limbs: 412 ± 65 μm 2 compared with 187 ± 17 μm 2 (p < 0.01). In vitro bone resorption experiments indicated that 2472 tumor cells had a limited ability to destroy bone in comparison with macrophages and osteoclasts. Taken in total, these findings define a model that is useful for the study of tumor osteolysis, and the data from analyses of the model demonstrate that the cellular mechanisms responsible for 2472 tumor‐induced osteolysis include both an increase in the number of osteoclasts and activation of mature osteoclasts.