Committed osteoclast precursors colonize the bone and improve the phenotype of a mouse model of autosomal recessive osteopetrosis

Alfredo Cappariello, Anna Concetta Berardi, Barbara Peruzzi, Andrea Del Fattore, Alberto Ugazio, Gian Franco Bottazzo, Anna Teti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)106-113
Number of pages8
JournalJournal of Bone and Mineral Research
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Bone resorption
  • Cell therapy
  • Osteoclast
  • Osteopetrosis
  • Stem cells

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

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