The role of bone-derived PDGF-AA in age-related pancreatic β cell proliferation and function

The occurrence of type 2 diabetes(T2D) increases with age. The platelet-derived growth factor (PDGF) is one of the key factors regulating β cell proliferation and function, but the contribution of PDGF signaling in β cells aging and senescence remains unexplored. Here, we showed that the level of both serum and tissue PDGF-AA decreased with age, and the serum PDGF-AA level was positively correlated with β cell proliferation and function in aging. The decline of PDGF-AA level in aging was partly due to decreased number as well as secretion of osteoblast lineage cells in bone tissue. Conditioned medium from osteoblast lineage cells induced insulinoma β cells proliferation and insulin secretion in vitro, while addition of PDGF-AA neutralizing antibody attenuated this effect. Transplantation of juvenile osteoblast lineage cells increased serum PDGF-AA level and promoted β cell proliferation and function in aging mice, which eventually resulted in better glucose tolerance. Taken together, these findings revealed the role of decreased bone-derived PDGF-AA in mediating the disrupted proliferation and function of β cells in aging.