Delayed osteoblast differentiation and altered inflammatory response around implants placed in incisor sockets of type 2 diabetic rats.
OBJECTIVE
Central to the process of osseointegration is the recruitment of mesenchymal progenitor cells to the healing site, their proliferation and differentiation to bone synthesising osteoblasts. The process is under the control of pro-inflammatory cytokines and growth factors. The aim of this study was to monitor these key stages of osseointegration and the signalling milieu during bone healing around implants placed in healthy and diabetic bone.


METHODS
Implants were placed into the sockets of incisors extracted from the mandibles of normal Wistar and diabetic Goto-Kakizaki rats. Mandibles 1-12 weeks post-insertion of the implant were examined by histochemistry and immunocytochemistry to localise the presence of Stro-1- positive mesenchymal progenitor cells, proliferating cellular nuclear antigen proliferative cells, osteopontin and osteocalcin, macrophages, pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and tumour growth factor (TGF)-β1. Image analysis provided a semi-quantification of positively expressing cells.


RESULTS
Histological staining identified a delay in the formation of mineralised bone around implants placed in diabetic animals. Within the diabetic bone, the migration of Stro-1 mesenchymal cells in the healing tissue appeared to be unaffected. However, in the diabetic healing bone, the onset of cell proliferation and osteoblast differentiation were delayed and subsequently prolonged compared with normal bone. Similar patterns of change were observed in diabetic bone for the presence of IL-1β, TNF-α, macrophages and TGF-β1.


CONCLUSIONS
The observed alterations in the extracellular presence of pro-inflammatory cytokines, macrophages and growth factors within diabetic tissues that correlate to changes in the signalling milieu, may affect the proliferation and differentiation of mesenchymal progenitor cells in the osseointegration process.
Mineralised Tissue Group, Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, Heath Park, Cardiff, UK.
John S
JS
Colombo
Deepak
D
Balani
Alastair J
AJ
Sloan
St John
SJ
Crean
Joji
J
Okazaki
Rachel J
RJ
Waddington
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D015921:Dental Implants; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007180:Incisor; D018836:Inflammation Mediators / Q000502:physiology*; D053583:Interleukin-1beta / Q000032:analysis; D008264:Macrophages / Q000473:pathology; D008297:Male; D008334:Mandible / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000473:pathology; D016348:Osseointegration / Q000502:physiology; D010006:Osteoblasts / Q000473:pathology*; D015675:Osteocalcin / Q000032:analysis; D010012:Osteogenesis / Q000502:physiology; D053495:Osteopontin / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020390:Tooth Socket / Q000473:pathology / Q000601:surgery*; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014945:Wound Healing / Q000502:physiology
D000954:Antigens, Surface; D015921:Dental Implants; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D018809:Proliferating Cell Nuclear Antigen; C527498:STRO-1 antigen, rat; C506897:Spp1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D053495:Osteopontin