• No results found

Bone and Cartilage Regeneration

N/A
N/A
Protected

Academic year: 2021

Share "Bone and Cartilage Regeneration"

Copied!
2
0
0

Loading.... (view fulltext now)

Full text

(1)

Bone and Cartilage Regeneration

Wnt Signaling Pathway in Healing

Akademisk avhandling

som för avläggande av medicine doktorsexamen vid Sahlgrenska Akademin vid Göteborgs Universitet kommer att offentligen försvaras i hörsal 2118, Hus 2, HVB,

Arvid Wallgrens backe, Göteborg Fredagen den 28 februari 2014 kl 09.00

av

Anna Thorfve

Fakultetsopponent: Professor Jan de Boer

MIRA Institute for Biomedical Techonology and Technical Medicine, Department of Tissue Regeneration, Faculty of Science and Technology

University of Twente, the Netherlands Avhandlingen baseras på följande delarbeten:

 

I. Thorfve. A, Dehne, T, Lindahl, A, Brittberg, M, Pruss. A, Ringe. J, Sittinger. M, and Karlsson. C, Characteristic Markers of the Wnt Sgnaling Pathways Are Differentially

Expressed in Osteoarthtitic Cartilage. Cartilage 2012; 3: 43-57.

II. Svala. E, Thorfve. A, Ley. C, Barreto Henriksson. H, Synnergren. J, Lindahl. A, Ekman. S, and Skiöldebrand. E, Effects of Interleukin-6 and Interleukin-1β on

Expression of Growth Differentiation Factor-5 and Wnt Signaling Pathway Genes in Equine Chondrocytes. Am J Vet Res 2014; 75: 132-140.

III. Thorfve. A, Lindahl. C, Xia. W, Igawa. K, Lindahl. A, Thomsen. P, Palmquist. A, and Tengvall. P, Hydroxyapatite Coating Affects the Wnt Signaling Pathway during

Peri-implant Healing in vivo. Acta Biomater 2014; 10: 1451-1462.

IV. Thorfve. A, Bergstrand. A, Ekström. K, Lindahl. A, Thomsen. P, Larsson. A, and Tengvall. P, Gene Expression Profiling of Peri-implant Healing of PLGA-Li+

Implants Reveals an Activated Wnt Signaling Pathway in vivo. In manuscript,

(2)

Bone and Cartilage Regeneration

Wnt Signaling Pathway in Healing

Anna Thorfve

Department of Biomaterials, Institute of Clinical Sciences

Sahlgrenska Academy at University of Gothenburg

Gothenburg, Sweden

Abstract

The Wnt signaling pathway plays a central role in bone and cartilage embryonic development, processes that are recapitulated during regeneration. Imbalance in such well conserved and complex system often contributes to numerous diseases, whereas controlled modulation of the Wnt signaling activity is an attractive target e.g. for improved fracture healing therapies. The first aim of the present thesis was to increase the knowledge of the underlying mechanisms that lead to cellular alterations in osteoarthritis (OA), resulting in cartilage degeneration. In particular, we investigated the genome-wide expression profile of Wnt related markers in human OA cartilage and the effect of the pro-inflammatory cytokines IL-1β and IL-6 in the context of Wnt signaling pathway, thereby revealing mechanisms for OA modulation therapies.

As a second aim, we studied if a local release of the canonical Wnt activator Li+ from hydroxyapatite (HA) or poly(lactic-co-glycolic acid) (PLGA) modulated the Wnt pathway and subsequently enhanced the bone regeneration around the implants.

The results indicated that the Wnt signaling pathways were dysregulated in OA cartilage, with a partly inhibited canonical Wnt signaling and an active non-canonical Wnt cascade. We were able to demonstrate that WNT5A was excessively expressed in degenerative cartilage, and that the pro-inflammatory cytokine IL-6 possessed cartilage protective properties by reducing β-catenin and canonical Wnt signaling. The canonical Wnt pathway was activated by HA but the osteoinductivity of HA itself overridden the Wnt modulating capacity of Li+. Finally, a global gene expression profiling demonstrated that the controlled release of Li+ from PLGA activated the canonical Wnt signaling.

In conclusion, the present findings may be used to develop gene targeted OA treatments and serve as a basis for further improvement of Li+ based therapies associated to fracture repair. This thesis sheds further light on the ambiguous influence of Wnt signaling in osteochondral homeostasis and repair mechanisms.    

Keywords: Wnt signaling pathway, osteoarthritis, bone regeneration, lithium ISBN: 978-91-628-8882-4

References

Related documents

46 Konkreta exempel skulle kunna vara främjandeinsatser för affärsänglar/affärsängelnätverk, skapa arenor där aktörer från utbuds- och efterfrågesidan kan mötas eller

The increasing availability of data and attention to services has increased the understanding of the contribution of services to innovation and productivity in

This is the concluding international report of IPREG (The Innovative Policy Research for Economic Growth) The IPREG, project deals with two main issues: first the estimation of

Närmare 90 procent av de statliga medlen (intäkter och utgifter) för näringslivets klimatomställning går till generella styrmedel, det vill säga styrmedel som påverkar

• Utbildningsnivåerna i Sveriges FA-regioner varierar kraftigt. I Stockholm har 46 procent av de sysselsatta eftergymnasial utbildning, medan samma andel i Dorotea endast

I dag uppgår denna del av befolkningen till knappt 4 200 personer och år 2030 beräknas det finnas drygt 4 800 personer i Gällivare kommun som är 65 år eller äldre i

Den förbättrade tillgängligheten berör framför allt boende i områden med en mycket hög eller hög tillgänglighet till tätorter, men även antalet personer med längre än

Industrial Emissions Directive, supplemented by horizontal legislation (e.g., Framework Directives on Waste and Water, Emissions Trading System, etc) and guidance on operating