Bovine milk kininogen fragment 1 center dot 2 promotes the proliferation of osteoblastic MC3T3-E1 cells

The active component on the proliferation of osteoblastic MC3T3-E1 cells wa s purified and identified from bovine milk. The growth-promoting activity w as measured by [H-3]thymidine incorporation on the cell. The purified prote in showed a molecular size of 17 kDa on SDS-PAGE. Its amino-terminal amino acid sequence was very similar to the internal sequence of bovine high mole cular weight (HMW) kininogen, which comprises fragment 1.2. The promotion o f proliferation was specific for osteoblastic MC3T3-E1 cells, not for fibro blast BALB/3T3 cells. In blood coagulation, HMW kininogen is considered to be cleaved by a specific enzyme kallikrein. HMW kininogen then releases two peptides, a biologically active peptide bradykinin and fragment 1.2, but t he fate of fragment 1.2 is unknown. This milk-derived protein that comprise s to fragment 1.2 showed a growth-promoting activity of osteoblasts. We pro pose the possibility that milk plays an important role in bone formation by supplying the active agent for osteoblasts as well as supplying calcium. ( C) 2000 Academic Press.