Abstract
Autosomal Recessive Osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast bone resorptive function (osteoclast-rich forms) or differentiation (osteoclast-poor forms). The latter form carries mutations in Tnfsf11 gene, which codifies for the receptor activator of NF-κB ligand (RANKL), an essential cytokine expressed in stromal cells. It contributes (with M-CSF) to the differentiation and activation of specialized osteoclasts from monocyte precursors in bone marrow niche. These patients, differently from other forms, do not benefit from HSC transplantation, demonstrating a pathogenetic role of stromal cells in unbalanced bone remodeling.
Highlights
Autosomal Recessive Osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast bone resorptive function or differentiation
In order to verify whether a defect in RANKL protein might cause an impairment in this compartment we generated bone marrow mesenchymal stromal cells (BM-MSC) from knockout mice
We analyzed the immune-phenotype using the following markers: CD45, CD34, CD9, SCA1, CD62L, CD117, CD44 and we observed a comparable phenotype despite a reduction in CD9 expression in Rankl-/- MSCs.We tested the clonogenic potential of KO MSCs and we observed a reduced capacity to form CFU, whereas the proliferation of ko MSCs was not different from the one of wt MSCs
Summary
Autosomal Recessive Osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast bone resorptive function (osteoclast-rich forms) or differentiation (osteoclast-poor forms) The latter form carries mutations in Tnfsf gene, which codifies for the receptor activator of NF-B ligand (RANKL), an essential cytokine expressed in stromal cells. It contributes (with M-CSF) to the differentiation and activation of specialized osteoclasts from monocyte precursors in bone marrow niche. These patients, differently from other forms, do not benefit from HSC transplantation, demonstrating a pathogenetic role of stromal cells in unbalanced bone remodeling
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