The Novel Pro-Osteogenic Activity of NUCB21-83

Abstract

NUCB21-83 has been recently reported as an anorexigenic and anti-hyperglycemic peptide. Here we report that NUCB21-83 promotes osteogenesis. It was found after two months of once-a-day intravenous injection of NUCB21-83, bone mineral density of femora and lumbar vertebrae were increased in ovariectomized rats. NUCB21-83 also increased the alkaline phosphatase activity and promoted mineralization in mouse MC3T3-E1 preosteoblastic cell line. When either both Arg60 and Arg63 or Ser72 were mutated to Ala, the pro-osteogenic activity was completely lost, indicating that these residues are structurally important for its biological function. Furthermore, it encumbered osteoclastic differentiation of RAW 264.7 macrophage. It also excluded any possibility of the effect caused by contaminants or experimental faults, and demonstrated that the pro-osteogenic activity observed was a specific effect of NUCB21-83 itself. These findings warranted that further studies on NUCB21-83 would be valuable for the treatment of bone metabolic diseases especially for osteoporosis. © 2013 Li et al.