title: Improving oral implant osseointegration in a murine model via Wnt signal amplification.
abstract: OBJECTIVE
  To determine the key biological events occurring during implant failure and then we use this knowledge to develop new biology-based strategies that improve osseointegration.
  
  
  METHODS
  Wild-type and Axin2(LacZ/LacZ) adult male mice underwent oral implant placement, with and without primary stability. Peri-implant tissues were evaluated using histology, alkaline phosphatase (ALP) activity, tartrate resistant acid phosphatase (TRAP) activity and TUNEL staining. In addition, mineralization sites, collagenous matrix organization and the expression of bone markers in the peri-implant tissues were assessed.
  
  
  RESULTS
  Maxillary implants lacking primary stability show histological evidence of persistent fibrous encapsulation and mobility, which recapitulates the clinical problems of implant failure. Despite histological and molecular evidence of fibrous encapsulation, osteoblasts in the gap interface exhibit robust ALP activity. This mineralization activity is counteracted by osteoclast activity that resorbs any new bony matrix and consequently, the fibrous encapsulation remains. Using a genetic mouse model, we show that implants lacking primary stability undergo osseointegration, provided that Wnt signalling is amplified.
  
  
  CONCLUSIONS
  In a mouse model of oral implant failure caused by a lack of primary stability, we find evidence of active mineralization. This mineralization, however, is outpaced by robust bone resorption, which culminates in persistent fibrous encapsulation of the implant. Fibrous encapsulation can be prevented and osseointegration assured if Wnt signalling is elevated at the time of implant placement.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA; Department of Periodontology, Service of Odontology, Rothschild Hospital, AP-HP, Paris 7 - Denis, Diderot University, U.F.R. of Odontology, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mouraret
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Claire
authors.initials: C
authors.lastname: Bardet
authors.forename: Antoine
authors.initials: A
authors.lastname: Popelut
authors.forename: John B
authors.initials: JB
authors.lastname: Brunski
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaussain
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000469:Alkaline Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000033:anatomy & histology; D000818:Animals; D060466:Axin Protein / Q000502:physiology; D001857:Bone Matrix / Q000473:pathology; D001862:Bone Resorption / Q000473:pathology; D002113:Calcification, Physiologic / Q000502:physiology; D003094:Collagen / Q000502:physiology; D003238:Connective Tissue / Q000473:pathology; D003758:Dental Implantation, Endosseous / Q000379:methods; D015921:Dental Implants; D019232:Dental Restoration Failure; D005355:Fibrosis; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008437:Maxilla / Q000033:anatomy & histology / Q000601:surgery; D051379:Mice; D023421:Models, Animal; D016348:Osseointegration / Q000502:physiology*; D010006:Osteoblasts / Q000201:enzymology / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D010519:Periodontium / Q000033:anatomy & histology; D010521:Periosteum / Q000033:anatomy & histology; D000071681:Tartrate-Resistant Acid Phosphatase; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; D015921:Dental Implants; D007527:Isoenzymes; D003094:Collagen; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Axin2; Wnt; bone; dental; fibrointegration; fibrous encapsulation; histology; in vivo; maxilla; mice; model; oral cavity