SEMINAR (Zoom)
This UC Next Seminar will be hosted online via Zoom. RSVP to receive the zoom link by emailing info@bioengineering.ucsb.edu.
Zoom will open after the host has joined at the start of each seminar. You can ask questions through the chat forum and by raising your "hand" and the speaker will call on you.
Speaker
Kevin Burt
9:25 am via ZOOM
Title: NF-κB Over-Activation Leads to Disc Degeneration and the Recruitment of Mechanoresponsive Macrophages
Abstract
Lower back pain is the leading cause of disability and is thought to be driven primarily by intervertebral disc degeneration (DD). Studies suggest DD is associated with increases in inflammatory and catabolic signaling and is characterized by a loss of structural integrity. Ultimately, this compromises disc mechanics and produces a loss of the primary mechanical force experienced within the disc, hydrostatic pressure (HP). Furthermore, infiltrating immune cells, such as monocyte/macrophages have been observed during DD. However, there is a gap in the knowledge of how inflammatory biological factors alone may initiate DD. Utilizing a connective tissue specific genetic mouse model, we evaluated how prolonged activation of NF-κB, a master transcription factor regulator of inflammatory responses and immune cell recruitment, affects disc health. Additionally, to identify the influence of the disc mechanical environment on invading immune cells, we evaluated the response of bone marrow derived macrophages to direct HP within a bioreactor system. We found NF-κB over-activation produced severe degeneration of the IVD with an increase in chemotactic proteins and recruitment of inflammatory macrophages. We also observed macrophages to be mechanoresponsive to healthy disc HP loading magnitudes via activation of an inflammatory resolving functional state. This was characterized by a distinct transcriptome profile, increased anti-inflammatory cytokine release, and phagocytic activity.
These findings provide evidence that NF-κB signaling is capable of producing severe DD in the absence of a physical injurious initiating event. Furthermore, within inflammatory over-activation and puncture injury models, we have identified multiple avenues, dictated via inflammatory signaling or tissue damage, in which innate immune cells are recruited to the IVD. Lastly, using a novel HP bioreactor system we have characterized an inflammatory resolving functional macrophage activated via healthy HP loading magnitudes. These findings suggest that a loss of pressurization within the disc may contribute to a lack of inflammatory resolution and frustrated healing.
BIO
Kevin Burt is currently a doctoral candidate in Biomedical Engineering at Columbia University. He earned his B.S. in Civil Engineering from Montana State University (2016) where his research focused on the use of microbial activity for hazardous waste water remediation. Now under the mentorship of Dr. Nadeen Chahine within Columbia’s Department of Orthopedic Surgery, his primary research evaluates the role of inflammatory transcription factor regulators and damage associated molecular patterns during intervertebral disc degeneration. Using in-vivo methods in genetically engineered mouse models and an in-vitro pressurized bioreactor he is investigating the pathology of biologically driven tissue degeneration and how innate immune cells react to the mechanical environment of the intervertebral disc. Expanding on his current work in mechanobiology and orthopedics, Kevin plans to further investigate how the changing mechanical microenvironments of musculoskeletal tissues dictate immune cell functionality.
