BMP-2 Gene-fibronectin-apatite Composite Layer Enhances Bone Formation

Overview

Journal J Biomed Sci

Publisher Biomed Central

Specialty Biology

Date 2011 Aug 24

PMID 21859498

Citations 11

Authors

Wei Zhang

Hideo Tsurushima

Ayako Oyane

Yushin Yazaki

Yu Sogo

Atsuo Ito

Akira Matsumura

Affiliations

Soon will be listed here.

Abstract

Background: Safe and efficient gene transfer systems are needed for tissue engineering. We have developed an apatite composite layer including the bone morphogenetic protein-2 (BMP-2) gene and fibronectin (FB), and we evaluated its ability to induce bone formation.

Methods: An apatite composite layer was evaluated to determine the efficiency of gene transfer to cells cultured on it. Cells were cultured on a composite layer including the BMP-2 gene and FB, and BMP-2 gene expression, BMP-2 protein concentrations, alkaline phosphatase (ALP) activity, and osteocalcin (OC) concentrations were measured. A bone defect on the cranium of rats was treated with hydroxyapatite (HAP)-coated ceramic buttons with the apatite composite layer including the BMP-2 gene and FB (HAP-BMP-FB). The tissue concentration of BMP-2, bone formation, and the expression levels of the BMP-2, ALP, and OC genes were all quantified.

Results: The apatite composite layer provided more efficient gene transfer for the cultured cells than an apatite composite layer without FB. The BMP-2 concentration was approximately 100-600 pg/mL in the cell-culture medium. Culturing the cells on the apatite composite layer for 27 days increased ALP activity and OC concentrations. In animal experiments, the tissue concentrations of BMP-2 were over 100 pg/mg in the HAP-BMP-FB group and approximately 50 pg/mg in the control groups. Eight weeks later, bone formation was more enhanced in the HAP-BMP-FB group than in the control groups. In the tissues surrounding the HAP button, the gene expression levels of ALP and OC increased.

Conclusion: The BMP-2 gene-FB-apatite composite layer might be useful for bone engineering.

Citing Articles

Tauroursodeoxycholic acid combined with selenium accelerates bone regeneration in ovariectomized rats.

Tao Z, Yang M, Shen C J Mater Sci Mater Med. 2024; 35(1):64.

PMID: 39404912 PMC: 11480188. DOI: 10.1007/s10856-024-06803-0.

Effects of the combination of bone morphogenetic protein-2 and nano-hydroxyapatite on the osseointegration of dental implants.

Pang K, Seo Y, Lee J J Korean Assoc Oral Maxillofac Surg. 2021; 47(6):454-464.

PMID: 34969019 PMC: 8721409. DOI: 10.5125/jkaoms.2021.47.6.454.

BMP-2 Gene Delivery-Based Bone Regeneration in Dentistry.

Park S, Kim K, Kim S, Lee Y, Seol Y Pharmaceutics. 2019; 11(8).

PMID: 31387267 PMC: 6723260. DOI: 10.3390/pharmaceutics11080393.

Fabrication of DNA-antibody-apatite composite layers for cell-targeted gene transfer.

Yazaki Y, Oyane A, Araki H, Sogo Y, Ito A, Yamazaki A Sci Technol Adv Mater. 2016; 13(6):064204.

PMID: 27877531 PMC: 5099764. DOI: 10.1088/1468-6996/13/6/064204.

When 1+1>2: Nanostructured composites for hard tissue engineering applications.

Uskokovic V Mater Sci Eng C Mater Biol Appl. 2015; 57:434-51.

PMID: 26354283 PMC: 4567690. DOI: 10.1016/j.msec.2015.07.050.

References

Gelse K, von der Mark K, Aigner T, Park J, Schneider H . Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells. Arthritis Rheum. 2003; 48(2):430-41. DOI: 10.1002/art.10759. View

Verma I, Somia N . Gene therapy -- promises, problems and prospects. Nature. 1997; 389(6648):239-42. DOI: 10.1038/38410. View

Chaudhari A, Ron E, Rethman M . Recombinant human bone morphogenetic protein-2 stimulates differentiation in primary cultures of fetal rat calvarial osteoblasts. Mol Cell Biochem. 1997; 167(1-2):31-9. DOI: 10.1023/a:1006853009828. View

Roy I, Mitra S, Maitra A, Mozumdar S . Calcium phosphate nanoparticles as novel non-viral vectors for targeted gene delivery. Int J Pharm. 2002; 250(1):25-33. DOI: 10.1016/s0378-5173(02)00452-0. View

Olmsted E, Blum J, Rill D, Yotnda P, Gugala Z, Lindsey R . Adenovirus-mediated BMP2 expression in human bone marrow stromal cells. J Cell Biochem. 2001; 82(1):11-21. DOI: 10.1002/jcb.1106. View

De Ranieri A, Virdi A, Kuroda S, Shott S, Dai Y, Sumner D . Local application of rhTGF-beta2 modulates dynamic gene expression in a rat implant model. Bone. 2005; 36(5):931-40. DOI: 10.1016/j.bone.2005.01.019. View

Petrie Aronin C, Sadik K, Lay A, Rion D, Tholpady S, Ogle R . Comparative effects of scaffold pore size, pore volume, and total void volume on cranial bone healing patterns using microsphere-based scaffolds. J Biomed Mater Res A. 2008; 89(3):632-41. PMC: 3122961. DOI: 10.1002/jbm.a.32015. View

Lieberman J, Daluiski A, Stevenson S, Wu L, McAllister P, Lee Y . The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats. J Bone Joint Surg Am. 1999; 81(7):905-17. DOI: 10.2106/00004623-199907000-00002. View

Silva R, Camilli J, Bertran C, Moreira N . The use of hydroxyapatite and autogenous cancellous bone grafts to repair bone defects in rats. Int J Oral Maxillofac Surg. 2005; 34(2):178-84. DOI: 10.1016/j.ijom.2004.06.005. View

10.

Park J, Gelse K, Frank S, von der Mark K, Aigner T, Schneider H . Transgene-activated mesenchymal cells for articular cartilage repair: a comparison of primary bone marrow-, perichondrium/periosteum- and fat-derived cells. J Gene Med. 2005; 8(1):112-25. DOI: 10.1002/jgm.826. View

11.

Oyane A, Murayama M, Yamazaki A, Sogo Y, Ito A, Tsurushima H . Fibronectin-DNA-apatite composite layer for highly efficient and area-specific gene transfer. J Biomed Mater Res A. 2009; 92(3):1038-47. DOI: 10.1002/jbm.a.32449. View

12.

Oyane A, Uchida M, Yokoyama Y, Choong C, Triffitt J, Ito A . Simple surface modification of poly(epsilon-caprolactone) to induce its apatite-forming ability. J Biomed Mater Res A. 2005; 75(1):138-45. DOI: 10.1002/jbm.a.30397. View

13.

Pompili A, Caroli F, Carpanese L, Caterino M, Raus L, Sestili G . Cranioplasty performed with a new osteoconductive osteoinducing hydroxyapatite-derived material. J Neurosurg. 1998; 89(2):236-42. DOI: 10.3171/jns.1998.89.2.0236. View

14.

Graham F, Van Der Eb A . A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973; 52(2):456-67. DOI: 10.1016/0042-6822(73)90341-3. View

15.

Nie H, Ho M, Wang C, Wang C, Fu Y . BMP-2 plasmid loaded PLGA/HAp composite scaffolds for treatment of bone defects in nude mice. Biomaterials. 2008; 30(5):892-901. DOI: 10.1016/j.biomaterials.2008.10.029. View

16.

Oyane A, Uchida M, Choong C, Triffitt J, Jones J, Ito A . Simple surface modification of poly(epsilon-caprolactone) for apatite deposition from simulated body fluid. Biomaterials. 2004; 26(15):2407-13. DOI: 10.1016/j.biomaterials.2004.07.048. View

17.

Shen H, Tan J, Saltzman W . Surface-mediated gene transfer from nanocomposites of controlled texture. Nat Mater. 2004; 3(8):569-74. DOI: 10.1038/nmat1179. View

18.

Sellers R, Zhang R, Glasson S, Kim H, Peluso D, DAugusta D . Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2). J Bone Joint Surg Am. 2000; 82(2):151-60. DOI: 10.2106/00004623-200002000-00001. View

19.

Benglis D, Wang M, Levi A . A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery. 2008; 62(5 Suppl 2):ONS423-31. DOI: 10.1227/01.neu.0000326030.24220.d8. View

20.

Fahim D, Whitehead W, Curry D, Dauser R, Luerssen T, Jea A . Routine use of recombinant human bone morphogenetic protein-2 in posterior fusions of the pediatric spine: safety profile and efficacy in the early postoperative period. Neurosurgery. 2010; 67(5):1195-204. DOI: 10.1227/NEU.0b013e3181f258ba. View