CAREER: A Role for Mechanics in Regulating Cellular Crosstalk within Intervertebral Joints of the Spine

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).

This Faculty Early Career Development (CAREER) award will support research on novel methods of mechanically regulated cellular communication in the spinal column. The research will focus on the intervertebral disc joint, a cushion-like structure between vertebrae, which provides mobility to the spinal column. This cushion also relies on diffusion of nutrients through the cartilage endplate.

Diseases of the intervertebral disc joint in the spinal column are complex in nature. It is difficult to isolate the specific pathology to one cell type or tissue. However, treatments targeting the intervertebral disc joint of the spine have commonly focused on a single tissue.

They do not target neighboring tissue structures such as the cartilage endplate, although lesions there are directly associated with joint disease. Recent studies provide evidence that the cartilage endplate is communicating with its surroundings. This suggests an active role for cartilage endplate in the tissue communication of the intervertebral disc joint.

This research award will build a foundation of new experimental knowledge on the active role of the cartilage endplate. Specifically, the biomechanical processes regulating cellular communication between tissues of the disc joint. The broader impacts of this research support a longer-term goal to identify better treatment for chronic joint diseases such as back pain.

The work will also address a critical need to educate ethnically diverse and socio-economically disadvantaged women students in STEM. The research will be directly integrated with the educational and outreach program. At the university and high school level, it will facilitate an understanding of musculoskeletal tissues via tissue engineering applications.

More broadly in human health, a program called “Skeleton School” will teach pre-school students how exercise influences our skeletal tissues.

The specific goal of this research is use novel cell-based human models to determine the effects of 1) specific mechanical microenvironmental conditions experienced within the disc joint (e.g., stiffness, compression or tension) on healthy and diseased human cartilage cell phenotype and secretion of extracellular vesicles; and 2) the effects of mechanically regulated cartilage endplate-derived extracellular vesicles on the composition and mechanical properties of extracellular matrix produced by human intervertebral disc cells in order to evaluate cartilage endplate-intervertebral disc crosstalk. In addition, the role of key mechano-sensors (TRPV ion channels/integrins) involved in mechanotransduction and the mechanical and protein profiles of human cartilage-endplate derived extracellular vesicles generated will be validated.

These experiments aim to target the complex mechano-biological interplay of “all tissue structures” within the disc joint focusing on a novel role for the cartilage endplate in joint physiology. This project will allow the PI to explore novel areas of mechanobiology centered on joint crosstalk and intercellular communication via mechanically regulated extracellular vesicles while establishing a long-term career in musculoskeletal mechanobiology and pathophysiology.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.