Alan Grodzinsky
Massachusetts Institute of Technology
Editor, Systems Biophysics
What are you currently working on?
We are developing an in vitro organ co-culture model of acute joint injuries that are known to cause post-traumatic osteoarthritis (PTOA) in normal, healthy, young to older humans following common sports injuries or accidents. Living osteochondral explants are freshly harvested from normal human donor knees, subjected to precise impact compressive loads in vitro (mimicking joint injury), and then co-cultured for weeks with joint capsule synovium explants obtained from the same human knees. Inflammatory cytokines and additional factors released from the synovium and cartilage-bone plugs lead to cell-mediated proteolytic breakdown of cartilage and weakened subchondral bone tissue. These sequelae initiate pathways known to occur in patients following tears of the anterior cruciate ligament and/or meniscus, leading to osteoarthritis (OA) in a high percentage of these patients within 10–20 years. There are currently no available drugs that can halt or reverse the progression of OA (or PTOA), only pain killers that have limited short-term effectiveness and no effects on the disease itself. Our objective is to use this organ culture system to identify mechanisms and pathways of joint tissue degradation and to test the efficacy of therapeutics to block OA/PTOA. Interestingly, exercise-related injuries are the most frequent source of injuries for astronauts living aboard the International Space Station (ISS). As part of the “Chips in Space Program” (supported by NIH-NCATS and the Center for Advancement of Science in Space [CASIS]), our organ co-culture model will be carried by SpaceX up to the ISS for a onemonth experiment during the next year to test the effects of microgravity and radiation on cartilage-bone degradation and the effectiveness of potential therapeutics to ameliorate such degradation. Taken together, this is an exciting combination for our group of interdisciplinary biophysical, biochemical, and cell biologic studies.
What have you read lately that you found really interesting or stimulating? (a paper, a book, science or not science)
Endurance: A Year in Space, A Lifetime of Discovery, by Scott Kelly, and Indivisible by Four: A String Quartet in Pursuit of Harmony, by Arnold Steinhardt (about the Guarneri String Quartet).
Who would you like to sit next to at a dinner party? (Scientist or not)
Michael Faraday!
At a cocktail party of non-scientists, how would you explain what you do?
Turns out to be a very common occurrence since, unfortunately, many people suffer from osteoarthritis in general, as well as the consequences of joint injuries occurring even at a young age. There is a visceral reaction to the description of tissue breakdown caused by osteoarthritis, and almost a demand to know what “cures” might be in the offing. This leads to the difficult discussion that, currently, there is no cure, and still no effective drugs (unlike the case for rheumatoid arthritis, for which there are now quite a few very successful blockbuster biologic drugs).