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Gene Expression Profiling of Peri-Implant Healing of PLGA-Li+ Implants Suggests an Activated Wnt Signaling Pathway In Vivo

Anna Thorfve ; Anna Bergstrand (Institutionen för kemi- och bioteknik, Farmaceutisk teknologi ; SuMo Biomaterials) ; Karin Ekström ; Anders Lindahl ; Peter Thomsen ; Anette Larsson (Institutionen för kemi- och bioteknik, Farmaceutisk teknologi ; SuMo Biomaterials) ; Pentti Tengvall
Plos One (1932-6203). Vol. 9 (2014), 7,
[Artikel, refereegranskad vetenskaplig]

Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li+). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+, while PLGA without Li+ was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li+ on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li+, with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li+ containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl. The presence of beta-catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors' knowledge the first report evaluating the effect of a local release of Li+ from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li+ in PLGA implants, Li+ is not an enhancer of early bone growth, although it affects the Wnt signaling pathway.


Article Number: e102597



Denna post skapades 2014-08-29. Senast ändrad 2016-04-04.
CPL Pubid: 202102

 

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Institutioner (Chalmers)

Institutionen för kliniska vetenskaper, sektionen för anestesi, biomaterial och ortopedi, Avdelningen för biomaterialvetenskap (GU)
Institutionen för kemi- och bioteknik, Farmaceutisk teknologi (2005-2014)
SuMo Biomaterials
Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin (GU)

Ämnesområden

Farmaceutisk synteskemi
Biomaterial

Chalmers infrastruktur