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.
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