Cibridos transmitocondriales como modelo "in vitro" para estudiar la asociación existente entre el ADN mitocondrial y la patología artrósica

Abstract

Osteoarthritis is a complex disease in which an imbalance between anabolic and catabolic processes leads to the anatomical and physiological alteration of the joint function. During the last years, mitochondrial function and genome have been associated with the incidence and/or progression of osteoarthritis. Nowadays, cell models such as transmitochondrial cybrids, which have the same nuclear background but different mitochondrial genome, are a useful tool to study the role of mitochondria in complex diseases like osteoarthritis. The aim of this thesis was to generate cells without mitochondrial genome and to establish transmitochondrial cybrids carrying the H and J haplogroups from healthy and osteoarthritic donors. This allowed us to study how the mitochondrial function may be related to mechanisms that initiate molecular alterations at the joint. Analyzing the parameters that have been related to osteoarthritis development, like oxidative stress, apoptosis, autophagy, glucose and fatty acid metabolism, we could demonstrate the relevance of functional mitochondria in the pathophysiology of osteoarthritis. To conclude, the results presented in this thesis showed that cybrids carrying different mitochondria genomes responded differently at functional and molecular levels.