Growth Factor Mechanobiology in the Synovial Joint
Connective tissues of the synovial joint (articular cartilage, meniscus, tendons, ligaments) face the onerous challenge of having to continuously maintain their structural integrity while faced with their intense, dynamic mechanical environment. It is well known that the synovial joint is filled with powerful anabolic growth factors that can signal cells to maintain and repair these tissues. However, remarkably, we still possess a limited understanding of the intrinsic mechanisms that exist to regulate and optimize growth factor activity in the context of day to day living.
A major aim of the Albro Lab’s research is the investigation of the mechanical loading environment's role on regulating the activity of growth factors in the synovial joint. This work is based on the foundational discovery of the Albro Lab that synovial joint mechanical forces can rapidly activate the latent complex of the powerful anabolic growth factor, transforming growth factor beta. This discovery suggests the existence of intriguing mechanobiological feeback mechansisms by which physiologic joint activity can give rise to TGF-beta activation, which in turn can signal cells to produce the extracellular matrix proteins needed for connective tissues to survive.
The Albro Lab currently has several ongoing research projects investigating the role of mechanical-induced TGF-beta activation in maintaining the synovial joint health. Our research suggests that this activation plays a multifaceted role in regulating the biosynthesis of key ECM components that are needed to ensure the robust mechanical performance of the synovial joint, including: 1) ECM proteins, that give rise to the structural integrity of connective tissues, and 2) bio-lubricants, that ensure low friction interfaces between moving tissues. Currently we are investigation how the efficacy of this mechanism may dissipate with aging and injury, thus contributing to degenerative pathology of the synovial joint.
TGF-beta resides in a latent molecular complex in the synovial joint that undergoes activation via physiologic mechanical shearing forces.
TGF-beta activation is shear-rate dependent, increasing with more rigorous physiologic joint activity.