Isolation and characterization of a novel peptide, osteoblast activating peptide (OBAP), associated with osteoblast differentiation and bone formation

Abstract A long-standing goal in bone loss treatment has been to develop bone-rebuilding anabolic agents that can potentially be used to treat bone-related disorders. To purify and isolate a novel anabolic that acts to osteoblasts, we monitored changes in intracellular calcium concentrations ([Ca 2+ ]i). We identified a novel, 24 amino-acid peptide from the rat stomach and termed this peptide osteoblast activating peptide (OBAP). Furthermore, we examined the effects of OBAP in osteoblasts . First, osteoblast differentiation markers (alkaline phosphatase [ALP], osteocalcin [OCN]) were analyzed using quantitative RT-PCR. We also examined the ALP activity in osteoblasts induced by OBAP. OBAP significantly increased the expression of osteoblast differentiation markers and the activity of ALP in vitro . Next, to address the in vivo effects of OBAP on bone metabolism, we examined the bone mineral density (BMD) of gastrectomized (Gx) rats and found that OBAP significantly increased BMD in vivo . Finally, to confirm the in vivo effects of OBAP on bone, we measured serum ALP and OCN in Gx rats and found that OBAP significantly increased serum ALP and OCN . Taken together, these results indicate that the novel peptide, OBAP, positively regulates bone formation by augmenting osteoblast differentiation. Furthermore, these results may provide a new therapeutic approach to anabolically treat bone-related disorders.