Fig. 4: Dynamic changes in metabolism to decreased extracellular arginine during RANKL-dependent osteoclastogenesis occur mTOR independently.
From: Environmental arginine controls multinuclear giant cell metabolism and formation
a RecArg1 exerts negligible effects on RANKL-mediated mTOR-related pathways. b Deficiency in mTOR/AA-starvation components cannot rescue effects of Arg-Depletion. Scale bar represents 200 µm. c–e Oxygen consumption rate (OCR), spare respiratory capacity (SRC) and basal glycolytic rate (ECAR) of preosteoclasts ± recArg1 (c, d n = 8). Negligible effects of arginine deprivation on preosteoclast 2-NBDG (glucose) uptake (e n = 4). All data 48 h post stimulation. f RANKL differentially changed metabolites intra-/extracellularly ± recArg1. Data normalized against M-CSF (left) and represent mean (n = 4, RANKL intracellular n = 3; see Supplementary Fig. 7c, d) g Transcriptional profiles of selected KEGG pathways. TCA cycle and serine/purine biosynthetic enzymes indicated. Data represent mean (n = 4). Significance levels according to empirical permutation test, empirical P-values reported. Data are mean ± SEM, *P < 0.05, ****P < 0.0001, one-way ANOVA post-hoc pairwise comparisons with Bonferroni correction (c–e) and two-way ANOVA post Sidak’s multiple comparisons test (c). Source data are provided as a Source Data file.
