Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter.
Mice with interleukin (IL)-7 transgene under the control of E(alpha) promoter over-express IL-7 in MHC class II-positive cells and develop specific immune phenotype, marked by an increase in CD45R(+) cells in both the bone marrow and peripheral blood. We show that IL-7 transgenic mice have a bone phenotype characterized by an age-related loss of trabecular bone in both axial and long bones. Osteopenia was the result of increased number of active osteoclasts on the surface of trabecular bone. Furthermore, IL-7 transgenic mice showed increased osteoclastic but unchanged osteoblastic potential of the bone marrow in vitro. IL-7 over-expression also created osteoclastogenic microenvironment within the bone marrow which promoted the commitment of precursors towards the osteoclast lineage. These findings are important for immunological disturbances where IL-7 is involved and where alterations in the immune system are accompanied by changes in bone metabolism, such as multiple myeloma, rheumatoid arthritis and postmenopausal osteoporosis.
Salopek
Daniela
D
Department of Oncology and Nuclear Medicine, Sisters of Mercy University Hospital, Zagreb, Croatia. d.salopek@gmail.com
Grcević
Danka
D
Katavić
Vedran
V
Kovacić
Natasa
N
Lukić
Ivan Kresimir
IK
Marusić
Ana
A
D000367:Age Factors; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D001862:Bone Resorption / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics
D015851:Interleukin-7; D017493:Leukocyte Common Antigens