Graphical summary of the experimental protocol: The different cell models (HOS, MG-63, Saos-2, TIG-121, TIG-108) were cultured for 24 hours in the Acidic or Neutral culture medium. Samples were obtained both from the cell lysates (Cells), and by using the culture supernatant (Medium). DNA, RNA, proteins and metabolites were extracted, and analysed by COBRA, RNA-seq, Western blots, and CE-TOFMS assays. The supernatant medium was also analyzed by CE-TOFMS assay for metabolomics screening to evaluate, together with the analysis on cell lysates, the accumulation, consumption, productive increase, or decrease rates relative to each metabolite.