Characterization of functional reprogramming during osteoclast development using quantitative proteomics and mRNA profiling.

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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.", "claims": [{"id": "claim-method", "statement": "The Pearson correlation was calculated for mRNA–protein pairs whose IO or OC mRNA expression levels were significantly different from those of OPs (p value < 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25044017", "locator": "sections[13] \"Protein and mRNA Correlation Analyses\" paragraph 2", "quote": "The Pearson correlation was calculated for mRNA–protein pairs whose IO or OC mRNA expression levels were significantly different from those of OPs (p value < 0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data have been deposited to the ProteomeXchange with identifier PXD000471.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25044017", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The data have been deposited to the ProteomeXchange with identifier PXD000471."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used Pearson’s correlation to compare transcript and protein expression changes; after filtering both datasets, the correlations were 0.50 for osteoclasts and 0.43 for intermediate osteoclasts. The underlying mass-spectrometry data were deposited in ProteomeXchange under identifier PXD000471.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25044017", "locator": "sections[24] \"A Cross-comparison of Transcriptome and Proteome Findings\" paragraph 5", "quote": "When we applied both the transcriptome and the proteome dataset filters together, the Pearson's correlation improved to 0.5 (OCs) and 0.43 (IOs), comparable to published data (18, 41–45)."}, {"asset": "source:pmid:25044017", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The data have been deposited to the ProteomeXchange with identifier PXD000471."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper used Pearson’s correlation to compare transcript and protein expression changes; after filtering both datasets, the correlations were 0.50 for osteoclasts and 0.43 for intermediate osteoclasts. 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