Development of Novel Models for Studying Osteoclasts

摘要: This thesis focuses on developing and characterizing novel models for studying osteoclasts with an emphasis how mutations abolishing osteoclastic acidification affect osteoclast signaling bone remodeling, as well to treat patients bearing these rare mutations. Bone remodeling is under normal circumstances a tightly balanced process where resorption of by followed adequate amounts formation osteoblasts.Mutations in the TCIRG1 gene lead severe autosomal recessive osteopetrosis (ARO) both mice man, characterized lack result abolished acid secretion, increased number non-resorbing osteoclasts, but or even formation. The first two papers are based studies adult transplanted stem cells from either osteoclast-rich osteopetrotic (oc/oc) osteoclast-poor (RANK KO). The paper cellular phenotype mouse model find that bones, bigger and, contrast endogenous oc/oc model, stronger compared wild type mice. In second we compare RANK KO mouse, maintaining vivo increases formation. third investigate role matrix, cell stage resorptive function mediated anabolic signaling. IV human ARO were investigated provide proof-of-principle lentiviral correction CD34+ derived patients. The results can be devided into exciting branges. Data obtained encourage further development molecules targeting when treating low mineral density diseases. Furthermore, correctional patient very promising, will serve basis clinical therapy osteopetrosis.