title: LIM domain protein-3 (LMP3) cooperates with BMP7 to promote tissue regeneration by ligament progenitor cells.
abstract: Gene transfer of key regulators of osteogenesis for mesenchymal stem cells represents a promising strategy to regenerate bone. It has been reported that LMP3, a transcription variant of LIM domain mineralization protein (LMP) lacking LIM domains, can induce osteogenesis in vitro and in vivo. As little is known about the effects of LMP3 gene therapy on periodontal ligament (PDL) cell osteogenic differentiation, this study sought to explore whether gene delivery of LMP3 can promote PDL cell mineralization and bone formation. Our results showed that adenoviral mediated gene transfer of LMP3 (AdLMP3) significantly upregulated ALP (Alkaline Phosphatase), BSP (Bone Sialoprotein) and BMP2 gene expression and increased in vitro matrix mineralization in human PDL. Although AdLMP3 gene delivery to PDL cells did not induce ectopic bone formation in vivo, we found that AdLMP3 augments new bone formation, which co-delivered with AdBMP7 gene transfer. Our study provides the evidence that there is a synergistic effect between LMP3 and BMP-7 in vivo, suggesting that LMP3 delivery may be used to augment BMP-mediated osteogenesis. LMP3 and BMP-7 combinatory gene therapy may also have specific applications for oral and periodontal regenerative medicine.
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.forename: H F
authors.initials: HF
authors.lastname: Rios
authors.forename: C-H
authors.initials: CH
authors.lastname: Park
authors.forename: A D
authors.initials: AD
authors.lastname: Taut
authors.forename: Q
authors.initials: Q
authors.lastname: Jin
authors.forename: J V
authors.initials: JV
authors.lastname: Sugai
authors.forename: P D
authors.initials: PD
authors.lastname: Robbins
authors.forename: W V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001857:Bone Matrix / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics* / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002460:Cell Line; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D010513:Periodontal Ligament / Q000166:cytology / Q000502:physiology*; D012038:Regeneration / Q000235:genetics*; D014170:Transformation, Genetic; D015854:Up-Regulation; D003598:Cytoskeletal Proteins; D048868:Adaptor Proteins, Signal Transducing
chemical_list: D000469:Alkaline Phosphatase; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D058574:Integrin-Binding Sialoprotein; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C525718:BMP2 protein, human; C525819:BMP7 protein, human; C484380:PDLIM7 protein, human; D003598:Cytoskeletal Proteins; D048868:Adaptor Proteins, Signal Transducing