Mechanisms and Therapeutic Approaches of Systemic Inflammation-impaired Bone Regeneration

Inflammation plays an essential role in bone healing. In the early stages of bone healing, inflammation resolution is beneficial for bone regeneration. However, chronic inflammation as occurs in diseases like obesity, diabetes mellitus, and rheumatoid arthritis hinder bone regeneration. The aim of the thesis was to investigate the adverse effects of systemic inflammation in the osteogenic differentiation of mesenchymal stem cells (MSCs) and bone regeneration. To this end, this thesis specifically aimed to investigate: 1) The effect of leptindeficient obesity on periodontal health. 2) The bone regenerative effect of the combination of low-dose BMP2 and leptin in leptin-deficient obesity. 3) The role and mechanisms of noncoding RNAs (ncRNAs), particularly of Mir155 and piR48444 in the regulation of osteogenic differentiation of MSCs in vitro and in bone regeneration in vivo under typical physiological and inflammatory conditions. Our results provide the fundamental insights and novel treatment options for bone regeneration in different inflammatory conditions.