title: Gene expression of inflammation and bone healing in peri-implant crevicular fluid after placement and loading of dental implants. A kinetic clinical pilot study using quantitative real-time PCR.
abstract: OBJECTIVE
  Early detection of healing complications after placement of dental implants is a pressing but elusive goal. This paper proposes a non-invasive diagnostic tool for monitoring healing- and peri-implant disease specific genes, complementary to clinical evaluations.
  
  
  METHODS
  Eighteen partially edentulous patients were recruited to this pilot study. Three Brånemark TiUnite® implants/patient (Nobel Biocare) were placed in a one-stage procedure. Abutments with smooth or rough (TiUnite®) surface were placed. The test group (n = 9) received fixed bridges (immediate loading), whereas the control group (n = 9) implants were loaded 3 months after surgery. In addition to clinical measurements, crevicular fluid was collected using paper strips at the implant abutments 2, 14, 28, and 90 days postoperative. mRNA was extracted, purified, and converted to cDNA. Quantitative PCR assays for IL-1β, TNF-α, Osteocalcin (OC), Alkaline Phosphatase (ALP), Cathepsin K, Tartrate Resistant Acid Phosphatase, and 18S ribosomal RNA were designed and validated. Relative gene expression levels were calculated.
  
  
  RESULTS
  One implant was lost in the control group and three in the test group. In one test patient, one implant showed lowered stability after 2 to 4 weeks and was unloaded. Later implant stability improved which allowed for loading after 3 to 4 months. TNF-α and ALP most commonly showed correlation with clinical parameters followed by IL-1β and OC. The strongest correlation was found for TNF-α with clinical complications at 2 and 14 days (p = .01/r = -048, and p = .0004/r = -0.56, respectively; test and control groups together). In some cases, gene expression predicted clinical complications (TNF-α, ALP, CK).
  
  
  CONCLUSIONS
  This study is based on samples from few individuals; still, some genes showed correlation with clinical findings. Further studies are needed to refine and optimize the sampling process, to find the appropriate panel, and to validate gene expression for monitoring implant healing.
authors.affiliation: The Institute for Postgraduate Dental Education, Jönköping, Sweden. christer.slotte@lj.se
authors.forename: Christer
authors.initials: C
authors.lastname: Slotte
authors.forename: Maria
authors.initials: M
authors.lastname: Lennerås
authors.forename: Catharina
authors.initials: C
authors.lastname: Göthberg
authors.forename: Felicia
authors.initials: F
authors.lastname: Suska
authors.forename: Neven
authors.initials: N
authors.lastname: Zoric
authors.forename: Peter
authors.initials: P
authors.lastname: Thomsen
authors.forename: Ulf
authors.initials: U
authors.lastname: Nannmark
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics; D016301:Alveolar Bone Loss / Q000209:etiology / Q000235:genetics*; D001861:Bone Regeneration / Q000235:genetics*; D000044:Dental Abutments; D003758:Dental Implantation, Endosseous / Q000009:adverse effects; D015921:Dental Implants / Q000009:adverse effects*; D003781:Denture Retention; D003830:Denture, Partial, Fixed; D015870:Gene Expression; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D006801:Humans; D057893:Immediate Dental Implant Loading; D007249:Inflammation / Q000235:genetics; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics; D015675:Osteocalcin / Q000032:analysis / Q000235:genetics; D057873:Peri-Implantitis / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D010865:Pilot Projects; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics; D014945:Wound Healing / Q000235:genetics
chemical_list: D015921:Dental Implants; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D000469:Alkaline Phosphatase