title: The mineralization inducing peptide derived from dentin sialophosphoprotein for bone regeneration.
abstract: Dentin sialophosphoprotein (DSPP) has been shown to play a primary role in the formation and growth of hydroxyapatite crystals in an extracellular matrix of hard tissue such as bone and teeth. We hypothesized that the mineralization ability of DSPP might depend on a specific domain within it. Three peptides, which have hydroxyapatite (HA) binding affinity, denoted as mineralization inducing peptide (MIP1, MIP2, and MIP3) were identified from DSPP. The both of MIP2 and MIP3 had HA nucleation activity demonstrated by XRD. Among three MIPs, MIP3 significantly supported the human bone marrow stromal cell differentiation into osteoblastic cells. An immunoblot with antibodies specific for the phosphorylated forms of ERK was conducted with cells treated by MIP3. MIP3 transduced intracellular signals via the ERK pathways and was able to induce osteoblastic differentiation, as seen by high expression of ALP, type 1 collagen, OC, OPN, and Runx2 in accordance with applied MIP3 concentration. The Asp, Glu, and Ser residues in MIP3 play important roles for the affinity of calcium in HA bone mineral. Further animal experiment with MIP3 in combination with hydroxyapatite mineral induced marked new bone formation for 4 weeks at rabbit calvarial defect model. The new bone area was much higher in test group, implying that the peptide modified group had excellent biocompatibility when compared with the unmodified group. Taken together, the MIP from DSPP has potential to enhance mineralization followed by to enhance osteoblastic differentiation and bone regeneration.
authors.affiliation: Dental Regenerative Biotechnology Major, Dental Research Institute and School of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Choi
authors.forename: Jue Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Suh
authors.forename: Gene
authors.initials: G
authors.lastname: Lee
authors.forename: Chong Pyoung
authors.initials: CP
authors.lastname: Chung
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects* / Q000235:genetics; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D017886:Durapatite / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020007:Implants, Experimental; D008297:Male; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010750:Phosphoproteins / Q000737:chemistry*; D011817:Rabbits; D012685:Sepharose; D012795:Sialoglycoproteins / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012886:Skull / Q000187:drug effects / Q000473:pathology; D000099311:Dentin Sialophosphoprotein
chemical_list: D000880:Anthraquinones; D017886:Durapatite; D016326:Extracellular Matrix Proteins; D010455:Peptides; D010750:Phosphoproteins; D012685:Sepharose; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C010078:alizarin