"The role of autophagy in chondrocyte survival, bone growth and osteoarthritis"
Speaker: Andrei Chagin, Assistant Professor, FyFa
Macro-autophagy (hereafter autophagy) is a process of catabolic degradation of damaged organelles and long-lived protein complexes. The process involves the formation of an autophagosome with a double membrane surrounding the material to be degraded. These autophagosomes fuse with lysosomes, where the contents are degraded and released into the cytosol. The main physiological function of autophagy is to facilitate cell survival during nutritional depletion. Additionally, autophagy is involved in numerous other processes such as cell death, intracellular clearance, anti-aging, cellular defense against microorganisms, tumor suppression etc.
The Chagin lab has generated mice with cartilage-specific ablation of autophagy indispensable gene Atg5 or Atg7 and explored chondrocyte physiology in development and aging.
Our results show that autophagy has a protective function in cartilage, preventing cell death. Mice without autophagy in their chondrocytes grow short and develop age-related osteoarthritis later in life. Both outcomes are associated with impaired chondrocyte survival and caspase-dependent apoptosis. Interestingly, starvation has very minor effect on autophagy-deficient mice or their bones, cultured ex vivo. Additionally, we found that some pharmacological inhibitors of autophagy can activate mTOR-signaling pathway in autophagy-independent and chondrocyte-specific manner causing growth stimulation. We have also explored the role of chaperone-mediated autophagy (CMA) utilizing Lamp2 KO mice and we not able to detect major role of CMA in cartilage physiology.
We conclude that autophagy is a protective mechanism in chondrocyte promoting their survival and defending against age-related osteoarthritis development.
Stockholm's Skeletal Seminars Series
The seminars aim to share recent data and common interest in skeletal biology and mineralized tissues as well as to build a platform for regular interactions between researchers and clinicians working in this area.Contact person: Andrei Chagin