title: Characterization of functional reprogramming during osteoclast development using quantitative proteomics and mRNA profiling.
abstract: In addition to forming macrophages and dendritic cells, monocytes in adult peripheral blood retain the ability to develop into osteoclasts, mature bone-resorbing cells. The extensive morphological and functional transformations that occur during osteoclast differentiation require substantial reprogramming of gene and protein expression. Here we employ -omic-scale technologies to examine in detail the molecular changes at discrete developmental stages in this process (precursor cells, intermediate osteoclasts, and multinuclear osteoclasts), quantitatively comparing their transcriptomes and proteomes. The data have been deposited to the ProteomeXchange with identifier PXD000471. Our analysis identified mitochondrial changes, along with several alterations in signaling pathways, as central to the development of mature osteoclasts, while also confirming changes in pathways previously implicated in osteoclast biology. In particular, changes in the expression of proteins involved in metabolism and redirection of energy flow from basic cellular function toward bone resorption appeared to play a key role in the switch from monocytic immune system function to specialized bone-turnover function. These findings provide new insight into the differentiation program involved in the generation of functional osteoclasts.
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: An
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Narayanan
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Manes
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 nitalazarau@niaid.nih.gov.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Nita-Lazar
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D053245:RANK Ligand / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D020543:Proteome; D053245:RANK Ligand