The mechanistic study of aging-associated Del-1 deficiency during resolution of a chronic inflammatory periodontal disease

• Applicant: Dr. Jong-Hyung Lim, Ph.D.
• Subject Area: Dentistry, Oral Surgery ; Immunology ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 417757362

Aging is associated with increased susceptibility to chronic inflammatory conditions, such as periodontal disease (PD). Mechanistic research on aging-related inflammation has therefore important implications. The host lab of the applicant recently linked reduced expression of the endogenous anti-inflammatory molecule, Del-1 (developmental endothelial locus-1) with aging-related PD. In addition, the host lab has preliminary evidence that aging-related Del-1 reduction may be associated with defective bone regeneration during periodontitis resolution, as Del-1 may act as a factor promoting osteoblastogenesis and formation of new alveolar bone.The effect of Del-1 on the ability of the periodontal ligament mesenchymal stromal/stem cells (MSCs) to proliferate and undergo osteogenic differentiation will be studied in the present proposal. Moreover, we will address whether aging-related Del-1 deficiency is causally linked with defective bone regeneration in PD. To this end, we will use in vitro differentiation assays and in vivo models of bone regeneration with appropriate genetically modified young and old mice including mice with global or cell-specific Del-1 deficiency. In addition, we plan to address whether local administration of Del-1 in old age can promote bone regeneration by rejuvenating the aged niche, which could point to Del-1 as a potential therapeutic approach in this context.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. George Hajishengallis