Overview
Induction of Early Stages of Osteoarthritis After Exposure to Microgravity (First Award Fellowship)
Principal Investigator:
Liliana Mellor, Ph.D.
Organization:
University of North Carolina/North Carolina State University
Technical Summary
The health of space crews during and after space missions has become a major concern of NASA. Several physiological changes have been associated with long-term exposure to microgravity, including skeletal muscles atrophy, immune system dysfunction, decreased nutrient intake, cardiovascular anomalies and bone density loss. One field that has yet to be explored is the possible effects of microgravity on the health of articular cartilage health, which is constantly exposed to mechanical forces under normal gravitational conditions on Earth. Disruption of cartilage homeostasis leads to pathological conditions such as arthritis, which according to the Center for Disease Control is the leading cause of disability in the United States.
Osteoarthritis (OA) is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage, and in advanced stages, can expose the highly innervated bone tissue, producing excruciating pain in the affected joint. Because of the limited regenerative capacity of articular cartilage, it is very important to detect early changes in the catabolic and anabolic rates that can lead to cartilage degradation.
This project’s goal is to investigate the effects of microgravity on cartilage homeostasis by exposing two chondrocyte cell lines to a modeled microgravity environment using a rotating wall vessel bioreactor. Cells exposed to microgravity will be compared to cells incubated under normal gravitational conditions as a control, as well as an arthritic-like cell model induced by treating chondrocytes with pro-inflammatory cytokines such as IL-1B and oncostatin M (OSM). Disruptions in cell-matrix interactions, changes in cytoskeletal morphology and gene up-regulation will be evaluated to determine changes in chondrocyte metabolism.
Hypothesis
Similar to bone, cartilage homeostasis can be compromised during exposure to microgravity, resulting in osteoarthritic-like conditions in astronauts after space missions.
This study will give a better insight to whether exposure to microgravity can make astronauts more prone to develop early osteoarthritis. In addition, since early stages of OA are hard to diagnose due to the lack of symptoms, the researchers also plan to investigate potential markers in the synovial fluid that can help detect early stages of OA.
Due to the limited capacity of regeneration in articular cartilage, early detection and treatment are key components to prevent the advanced stages of cartilage degradation, which is the leading cause of disability in the U.S., limiting the activities of nearly 21 million adults.