Stromal cell-derived factor-1 (SDF-1) is a cytokine that is important in stem and progenitor cell recruitment in tissue repair after injury. Regenerative procedures using collagen membranes (CMs) are presently well established in periodontal and implant dentistry. The objective of this study is to test the subsequent effects of the released SDF-1 from a CM on bone regeneration compared to platelet-derived growth factor (PDGF) in vitro and in vivo. For in vitro studies, cell proliferation, alkaline phosphatase activity, and osteoblastic differentiation marker genes were assessed after MC3T3-E1 mouse preosteoblasts were cultured with CMs containing factors. In vivo effects were investigated by placement of CMs containing SDF-1 or PDGF using a rat mandibular bone defect model. At 4 weeks after the surgery, the new bone formation was measured using micro-computed tomography (µCT) and histological analysis. The results of in vitro studies revealed that CM delivery of SDF-1 significantly induced cell proliferation, ALP activity, and gene expression of all osteogenic markers compared to the CM alone or control, similar to PDGF. Quantitative and qualitative µCT analysis for volume of new bone formation and the percentage of new bone area showed that SDF-1-treated groups significantly increased and accelerated bone regeneration compared to control and CM alone. The enhancement of bone formation in SDF-1-treated animals was dose-dependent and with levels similar to those measured with PDGF. These results suggest that a CM with SDF-1 may be a great candidate for growth factor delivery that could be a substitute for PDGF in clinical procedures where bone regeneration is necessary.
HämmerleCHLangNP. Single stage surgery combining transmucosal implant placement with guided bone regeneration and bioresorbable materials. Clin Oral Implants Res2001; 12: 9–18.
2.
GreenwellH. Position paper: guidelines for periodontal therapy. J Periodontol2001; 72: 1624–1628.
3.
ShinSYParkHNKimKH. Biological evaluation of chitosan nanofiber membrane for guided bone regeneration. J Periodontol2005; 76: 1778–1784.
4.
DahlinCLindeAGottlowJ. Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg1988; 81: 672–676.
5.
LindeAAlberiusPDahlinC. Osteopromotion: a soft-tissue exclusion principle using a membrane for bone healing and bone neogenesis. J Periodontol1993; 64: 1116–1128.
6.
BehringJJunkerRWalboomersXF. Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. A systematic review. Odontology2008; 96: 1–11.
7.
LuHKLeeSYLinFP. Elastic modulus, permeation time and swelling ratio of a new porcine dermal collagen membrane. J Periodontol Res1998; 33: 243–248.
8.
PatinoMGNeidersMEAndreanaS. Collagen as an implantable material in medicine and dentistry. J Oral Implantol2002; 28: 220–225.
9.
YamanoSLinTYDaiJ. Bioactive collagen membrane as a carrier of sustained release of PDGF. J Tissue Sci Eng2011; 2: 110.
10.
WeiGJinQGiannobileWV. Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB. J Control Release2006; 112: 103–110.
11.
Le GrandEK. Preclinical promise of becaplermin (rhPDGF-BB) in wound healing. Am J Surg1998; 176: 80S–82S.
12.
CaplanAICorreaD. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs. J Orthop Res2011; 29: 1795–1803.
13.
SimionMRocchiettaIKimD. Vertical ridge augmentation by means of deproteinized bovine bone block and recombinant human platelet-derived growth factor-BB: a histologic study in a dog model. Int J Periodontics Restorative Dent2006; 26: 415–423.
14.
NevinsMGarberDHanrattyJJ. Human histologic evaluation of anorganic bovine bone mineral combined with recombinant human platelet-derived growth factor BB in maxillary sinus augmentation: case series study. Int J Periodontics Restorative Dent2009; 29: 583–591.
15.
WallaceSCSnyderMBPrasadH. Postextraction ridge preservation and augmentation with mineralized allograft with or without recombinant human platelet-derived growth factor BB (rhPDGF-BB): a consecutive case series. Int J Periodontics Restorative Dent2013; 33: 599–609.
16.
NevinsMGiannobileWVMcGuireMK. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol2005; 76: 2205–2215.
17.
YamanoSHakuKYamanakaT. The effect of a bioactive collagen membrane releasing PDGF or GDF-5 on bone regeneration. Biomaterials2014; 35: 2446–2453.
18.
YoungCSLaddPABrowningCF. Release, biological potency, and biochemical integrity of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) combined with AugmentTM Bone Graft or GEM 21S beta-tricalcium phosphate (β-TCP). J Control Release2009; 140: 250–255.
19.
BuxtonPEdwardsCArcherCW. Growth/differentiation factor-5 (GDF-5) and skeletal development. J Bone Joint Surg Am2001; 83A: S23–S30.
20.
MatsudaNLinWLKumarNM. Mitogenic chemotactic, and synthetic responses of rat periodontal ligament fibroblastic cells to polypeptide growth factors in vitro. J Periodontol1992; 63: 515–525.
21.
PoyntonARLaneJM. Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine2002; 27: S40–S48.
22.
HarwoodPJGiannoudisPV. Application of bone morphogenetic proteins in orthopaedic practice: their efficacy and side effects. Expert Opin Drug Saf2005; 4: 75–89.
23.
ZhangGNakamuraYWangX. Controlled release of stromal cell-derived factor-1 alpha in situ increases c-kit + cell homing to the infarcted heart. Tissue Eng2007; 13: 2063–2071.
24.
JinDKShidoKKoppHG. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4 + hemangiocytes. Nat Med2006; 12: 557–567.
25.
BaggiooliniM. Chemokines and leukocyte traffic. Nature1998; 392: 565–568.
26.
YuXHuangYCollin-OsdobyP. Stromal cell-derived factor-1 (SDF-1) recruits osteoblast precursors by inducing chemotaxis, matrix metalloproteinase-9 (MMP-9) activity, and collagen transmigration. J Bone Miner Res2003; 18: 1404–1418.
27.
DuLYangPGeS. Stromal cell-derived factor-1 significantly induces proliferation, migration, and collagen type 1 expression in a human periodontal ligament stem cell subpopulation. J Periodontol2012; 83: 379–388.
28.
DaiJJianJBoslandM. Roles of hormone replacement therapy and iron in proliferation of breast epithelial cells with different estrogen and progesterone receptor status. Breast2008; 17: 172–179.
29.
ArtziZGivolNRohrerMD. Qualitative and quantitative expression of bovine bone mineral in experimental bone defects. Part 1: description of a dog model and histological observations. J Periodontol2003; 74: 1143–1152. .
30.
KabanLBGlowackiJMurrayJE. Repair of experimental mandibular bony defects in rats. Surg Forum1979; 30: 519–521.
31.
LivakKJSchmittgenTD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods2001; 25: 402–408.
32.
RatanavarapornJFuruyaHKoharaH. Synergistic effects of the dual release of stromal cell-derived factor-1 and bone morphogenetic protein-2 from hydrogels on bone regeneration. Biomaterials2011; 32: 2797–2811.
33.
SatoRMatsuzakaKKokubuE. Immediate loading after implant placement following tooth extraction up-regulates cellular activity in the dog mandible. Clin Oral Implants Res2011; 22: 1372–1378.
34.
AndrewJGHoylandJAFreemontAJ. Platelet-derived growth factor expression in normally healing human fractures. Bone1995; 16: 455–460.
35.
LiebermanJRDaluiskiAEinhornTA. The role of growth factors in the repair of bone biology and clinical applications. J Bone Joint Surg Am2002; 84: 1032–1044.
36.
HosoganeNHuangZRawlinsBA. Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells. Int J Biochem Cell Biol2010; 42: 1132–1141.
37.
ZhuWBoachie-AdjeiORawlinsBA. A novel regulatory role for stromal derived factor-1 signaling in bone morphogenetic protein-2 osteogenic differentiation of mesenchymal C2C12 cells. J Biol Chem2007; 282: 18676–18685.
38.
ZhuWLiangGHuangZ. Conditional inactivation of the CXCR4 receptor in osteoprecursors reduces postnatal bone formation due to impaired osteoblast development. J Biol Chem2011; 286: 26794–26805.
39.
MarkMPPrinceCWOosawaT. Immunohistochemical demonstration of 44 KD phosphoprotein in developing rat bones. J Histochem Cytochem1987; 35: 707–715.
40.
ButlerWT. The nature and significance of osteopontin. Connect Tissue Res1989; 23: 123–136.
41.
YaoKLTodescanRJrSodekJ. Temporal changes in matrix protein synthesis and mRNA expression during mineralized tissue formation by adult rat bone marrow cells in culture. J Bone Miner Res1994; 9: 231–240.
42.
SodekJChenJNagataT. Regulation of osteopontin expression in osteoblasts. Ann N Y Acad Sci1995; 760: 223–241.
43.
ZoharRLeeWAroraP. Single cell analysis of intracellular osteopontin in osteogenic cultures of fetal rat calvarial cells. J Cell Physiol1997; 170: 88–100.
44.
OwenTAAronowMShalhoubV. Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Physiol1990; 143: 420–430.
45.
WeberGFAshkarMJGlimcherMJ. Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science1996; 271: 509–512.
46.
PeledAPetitIKolletO. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science1999; 283: 845–848.
47.
ZhouBHanZCPoonMC. Mesenchymal stem/stromal cells (MSC) transfected with stromal derived factor 1 (SDF-1) for therapeutic neovascularization: enhancement of cell recruitment and entrapment. Med Hypotheses2007; 68: 1268–1271.
48.
BryanDWalkerKBFergusonM. Cytokine gene expression in a murine wound healing model. Cytokine2005; 31: 429–438.
49.
JiJFHeBPDheenST. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells2004; 22: 415–427.
50.
HillWDHessDCMartin-StuddardA. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol2004; 63: 84–96.
51.
RatajczakMZMajkaMKuciaM. Expression of functional CXCR4 by muscle satellite cells and secretion of SDF-1 by muscle-derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and hematopoietic stem/progenitor cells in muscles. Stem Cells2003; 21: 363–371.
52.
CeradiniDJKulkarniARCallaghanMJ. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med2004; 10: 858–864.
53.
KitaoriTItoHSchwarzEM. Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis Rheum2009; 60: 813–823.
54.
OtsuruSTamaiKYamazakiT. Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway. Stem Cells2008; 26: 223–234.
55.
KapasSClarkAJ. Identification of an orphan receptor gene as a type I calcitonin gene-related peptide receptor. Biochem Biophys Res Commun1995; 217: 832–838.
56.
MiaoZLukerKESummersBC. CXCR7 (RDC1) promotes breast and lung tumor growth in vitro and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA2007; 104: 15735–15740.
57.
SierroFBibenCMartinez-MunozL. Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc Natl Acad Sci USA2007; 104: 14759–14764.
58.
KleinheinzJStratmannUJoosU. VEGF-activated angiogenesis during bone regeneration. J Oral Maxillofac Surg2005; 334: 561–568.
59.
SalcedoRWassermanKYoungHA. Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial: in vivo neovascularization induced by stromal-derived factor-1. Am J Pathol1999; 154: 1125–1135.
60.
ThevenotPTNairAMShenJ. The effect of incorporation of SDF-1α into PLGA scaffolds on stem cell recruitment and the inflammatory response. Biomaterials2010; 31: 3997–4008.
61.
KimuraYTabataY. Controlled release of stromal cell-derived factor-1 from gelatin hydrogels enhances angiogenesis. J Biomater Sci Polym Ed2010; 21: 37–51.
62.
YamaguchiJKusanoKFMasuoO. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation2003; 107: 1322–1328.
63.
BalabanianKLaganeBInfantinoS. The chemokine SDF-1/CXCR12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem2005; 280: 35760–35766.
64.
RaggoCRuhlRMcAllisterS. Novel cellular genes essencial for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. Cancer Res2005; 65: 5084–5095.
65.
LiuHLiMDuL. Local administration of stromal cell-derived factor-1 promotes stem cell recruitment and bone regeneration in a rat periodontal bone defect model. Mater Sci Eng C Mater Biol Appl2015; 53: 83–94.
66.
WeiJFangYJinlingM. Incorporation of stromal cell-derived factor-1α in PCL/gelatin electrospun membranes for guided bone regeneration. Biomaterials2013; 34: 735–745.
