This application proposes experimentation designed to identify the cell and cellular mechanism responsible for bone resorption during tumor osteolysis. Tumor osteolysis occurs when primary or metastatic malignancies are present in bone and cause bone destruction. Clinically, this process results in pain, decreased mobility, hypercalcemia, anemia and skeletal fracture. Deficiencies in prevention, early detection and treatment underscore the fact that knowledge defining the biology of tumor osteolysis is scarce. Specifically neither the cell nor the cellular mechanism responsible for tumor osteolysis has been identified. Research proposed within this application is designed to identifying the cell and cellular mechanism which are responsible for bone resorption during tumor osteolysis. The experimentation which is proposed will 1) study tumor osteolysis with an in vivo murine model, 2) study tumor osteolysis with an in vitro murine model, and 3) study tumor osteolysis from human tumor cells in vivo (using athymic mice) and in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AR001909-01
Application #
3079377
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1993-08-10
Project End
1998-07-31
Budget Start
1993-08-10
Budget End
1994-07-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Clohisy, D R; Perkins, S L; Ramnaraine, M L (2000) Review of cellular mechanisms of tumor osteolysis. Clin Orthop Relat Res :104-14
Clohisy, D R; Ramnaraine, M L (1998) Osteoclasts are required for bone tumors to grow and destroy bone. J Orthop Res 16:660-6
Ramnaraine, M L; Clohisy, D R (1998) Evaluation of mutant mouse production by mice that are heterogeneous for the Mcfsop gene. Lab Anim Sci 48:300-2
Clohisy, D R; Ramnaraine, M L (1997) Osteoclast formation during tumor osteolysis does not require proliferating osteoclast precursor cells. J Orthop Res 15:301-6
Clohisy, D R; Ogilvie, C M; Carpenter, R J et al. (1996) Localized, tumor-associated osteolysis involves the recruitment and activation of osteoclasts. J Orthop Res 14:2-6
Clohisy, D R; Palkert, D; Ramnaraine, M L et al. (1996) Human breast cancer induces osteoclast activation and increases the number of osteoclasts at sites of tumor osteolysis. J Orthop Res 14:396-402
Clohisy, D R; Ogilvie, C M; Ramnaraine, M L (1995) Tumor osteolysis in osteopetrotic mice. J Orthop Res 13:892-7