Figure 1C depicts the contradictory findings of VIP-mediated effects on osteoblasts. The conflicting data might result from the different origin of cell types used in the respective studies. Probably, osteosarcoma cell lines are derived from abnormal bone cells and reactions and mechanisms studied in these cell types may, in part, not reflect physiological reactions. Apart from bone, PACAP expression was detected in osteoclasts and osteoblasts in the periodontal ligaments after tooth luxation indicating a role for this neuropeptide in the tooth microenvironment [127]. Here, ADCYAP1 is linked to osteosarcoma.