Serum NT/CT SIRT1 ratio reflects early osteoarthritis and chondrosenescence

Abstract Objective: Previous work has established that the deacetylase sirtuin-1 (SIRT1) is cleaved by cathepsin B in chondrocytes subjected to proinflammatory stress, yielding a stable but inactive N-terminal (NT) polypeptide (75SIRT1) and a C-terminal (CT) fragment. The present work examined if chondrocyte-derived NT-SIRT1 is detected in serum and may serve as an investigative and exploratory biomarker of osteoarthritis (OA). Methods: We developed a novel ELISA assay to measure the ratio of NT to CT of SIRT1 in the serum of human individuals and mice subjected to post-traumatic OA (PTOA) or age-dependent OA (ADOA). We additionally monitored NT/CT SIRT1 in mice subject to ADOA/PTOA followed by senolytic clearance. Human chondrosenescent and non-senescent chondrocytes were exposed to cytokines and analysed for apoptosis and NT/CT SIRT1 ratio in conditioned medium. Results: Wild-type mice with PTOA or ADOA of moderate severity exhibited increased serum NT/CT SIRT1 ratio. In contrast, this ratio remained low in cartilage-specific Sirt1 knockout mice despite similar or increased PTOA and ADOA severity. Local clearance of senescent chondrocytes from old mice with post-traumatic injury resulted in a lower NT/CT ratio and reduced OA severity. While primary chondrocytes exhibited NT/CT ratio increased in conditioned media after prolonged cytokine stimulation, this increase was not evident in cytokine-stimulated chondrosenescent cells. Finally, serum NT/CT ratio was elevated in humans with early-stage OA. Conclusions: Increased levels of serum NT/CT SIRT1 ratio correlated with moderate OA in both mice and humans, stemming at least in part from non-senescent chondrocyte apoptosis, possibly a result of prolonged inflammatory insult

Verhaltensmedizin, Psychotherapie und Zahnheilkunde

Biological, psychological and social processes are of relevance in the development and treatment of dental disorders. However, knowledge about interactions among these factors has only few implications for clinical practice. Hence, the goal of this article is to provide an overview of the links between behavioral medicine, psychotherapy and dentistry. The biobehavioral implications of different dental illnesses and disorders (caries, gingivitis, periodontitis, burning-mouth syndrome, and halitosis) as well as biobehavioral characteristics of specific patient groups are presented. The existing scientific knowledge in the interdisciplinary field of behavioral medicine, psychotherapy and dentistry provides the basis for a variety of treatment approaches. Its efficacy has, in part, already been confirmed. The integration of knowledge on psychobiological processes underlying psychotherapy and dental illnesses may lead to new interventions, based on the concept of neuropsychotherapy. It can be expected that further studies on the efficacy and effectiveness of specific biobehavioral interventions will significantly contribute to an increase in oral health