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Committed osteoclast precursors colonize the bone and improve the phenotype of a mouse model of autosomal recessive osteopetrosis
Author(s) -
Cappariello Alfredo,
Berardi Anna Concetta,
Peruzzi Barbara,
Del Fattore Andrea,
Ugazio Alberto,
Bottazzo Gian Franco,
Teti Anna
Publication year - 2010
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.090715
Subject(s) - osteopetrosis , osteoclast , bone marrow , bone resorption , haematopoiesis , multinucleate , stem cell , pathology , phenotype , bone remodeling , medicine , biology , immunology , cancer research , microbiology and biotechnology , genetics , receptor , gene
Osteopetrosis is a genetic disease characterized by defective osteoclasts. Autosomal recessive osteopetrosis is fatal within the first years of life. Hematopoietic stem cell transplantation (HSCT) cures fewer than 50% of cases but often leaves severe neurologic damages and other dysfunctions. Osteoclast appearance after HSCT is a slow process, during which disease progression continues. We hypothesize that a support osteoclast precursor therapy may contribute to improve the osteopetrotic phenotype. To this end, we established a procedure to obtain the best yield of osteoclast precursors from human peripheral blood or mouse bone marrow mononuclear cells. These cells were injected in vivo in animal models, testing different cell injection protocols, as well as in association with CD117+ stem cells. Injected cells showed the ability to form multinucleated osteoclasts and to improve the phenotype of oc/oc osteopetrotic mice. In the best working protocol, animals presented with longer survival, improved weight and longitudinal growth, increased tibial length, tooth eruption, decreased bone volume, reduced bone marrow fibrosis, and improved hematopoiesis compared with sham‐treated mice. These results provide first‐hand information on the feasibility of a support osteoclast precursor therapy in osteopetrosis. © 2010 American Society for Bone and Mineral Research