title: The novel pro-osteogenic activity of NUCB2(1-83.).
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.
authors.affiliation: Institute of Molecular Medicine, Nanjing University, Nanjing, China.
authors.forename: Ruishu
authors.initials: R
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wenbo
authors.initials: W
authors.lastname: Jin
authors.forename: Xinfang
authors.initials: X
authors.lastname: Yuan
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Wu
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Tan
authors.forename: Feng
authors.initials: F
authors.lastname: Bi
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Liu
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D000080866:Nucleobindins; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D010446:Peptide Fragments / Q000494:pharmacology*; D053245:RANK Ligand / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D010446:Peptide Fragments; D053245:RANK Ligand; D012333:RNA, Messenger; D000469:Alkaline Phosphatase