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The tissue-destroying inflammation- Who is susceptible and how do we prevent or slow it down?

Research project The mechanisms behind inflammation-induced bone loss, where bone resorption exceeds bone formation, are not well understood. We explore molecular factors that control the bone remodelling processes with special interest in chemokines. It is largely unknown why some individuals are more prone to develop bone loss due to inflammation, as in periodontitis and peri-implantitis. We utilize a large periodontitis cohort, with blood and clinical data, to identify genetic factors behind periodontitis.

Inflammation-induced bone loss is a hallmark of periodontitis and peri-implantitis. Tooth loss due to periodontitis is stressful for the affected individual and dental implants, as replacement for lost teeth, are not a final solution as inflammation-induced bone-loss also affects implants. Therefore, prevention of inflammation-induced bone loss presents a possible target for future treatment strategies, but further research is warranted. Moreover, identification of genetic- and biological markers is warranted to help us identify individuals at risk of developing disease.

Head of project

Pernilla Lundberg
Professor, senior consultant dentist
E-mail
Email

Project overview

Project period:

2020-01-01 2025-01-01

Participating departments and units at Umeå University

Department of Odontology

Research subject

Odontology

External funding

Region Västerbotten

Project description

Mechanisms of inflammation-induced bone loss

Inflammation disrupts the equilibrium between bone forming osteoblasts and bone resorbing osteoclasts, resulting in pathological bone loss, which is seen in periodontitis, peri-implantitis, osteoporosis and rheumatoid arthritis.  In order to find new methods to prevent or treat pathological bone loss, it is crucial to identify underlying mechanisms that leads to increased bone resorption. Increasing evidence suggest that a group of molecules named chemokines play important roles in normal and pathological bone remodeling. We recently discovered that individuals with periodontitis have higher serum levels of the chemokine CCL11. Furthermore, we showed that CCL11 is released from osteoblasts during inflammation and that CCL11 has a stimulatory effect on migration of pre-osteoclasts and enhances bone resorption.

 

We utilize a range of model systems to further explore the role of chemokines and chemokine receptors in inflammation-induced bone resorption. We study effects of chemokine signaling in cell cultures of osteoblasts and osteoclasts in vitro. More specifically, we analyze changes in gene- and protein expression that can be linked to cell executive functions. Furthermore, we use an in vivo model of inflammation-induced bone loss and advanced bone microtomographic and histomorphometric analysis methods to explore the importance of chemokine signaling during bone homeostasis and pathology. We aim to find new chemokine signaling pathways that could serve as potential targets for medical intervention.

 

Studying periodontitis and peri-implantitis

Bone loss in periodontitis is triggered by inflammation in the gums. Locally produced inflammatory molecules are distributed systemically by circulation and research demonstrates a connection between periodontitis and several other diseases, a highly interesting research field in which postdocs CKH and EK pursue their respective projects. The onset and severity of periodontitis is partly explained by a genetic susceptibility and today we have no methods to identify individuals at risk. Dental implants, as replacement for lost teeth, are not a final solution as they are also affected by bone loss.

 

In our Periogene North cohort exceeding 1000 individuals, we examine blood, exudate and tissue samples from individuals with or without periodontitis and peri-implantitis. Our aim is to detect and identify genetic- and biological markers that could be used as diagnostic and/or prognostic tools. Our research also includes randomized controlled treatment studies of periodontitis and peri-implantitis through postdocs CI and AH.

Links

Listen to prof. Pernilla Lundberg as she describes her research

Read more about WCMM associated researcher, Cecilia Koskinen-Holms project on periodontitis in Ehler-Danlos syndrome

Read more about WCMM associated researcher, Elin Kindstedts project on the association between periodontitis and rheumatoid arthritis

External funding