Joint Trauma and Lubricin
doggedly pursuing his research into lubricin, a naturally occurring protein in
the body, for more than 30 years. Read his story.
Lubricin is a mucinous glycoprotein that provides lubricating properties within synovial joints. It is synthesized by cells lining synovial joints, including synovial cells, superficial zone chondrocytes and tendon cells. The lubricating properties of the molecules have been studied in several laboratories and have been shown to reduce the coefficient of friction in cartilage-on-glass, rubber-on-glass, and cartilage-on-cartilage test systems.
Important Findings
A PRG4 mouse colony exists at Rhode Island Hospital which has provided important insights into the role of lubrication in chondroprotection. We recently established that the absence of this protein leads to premature and significant joint wear (Jay, et al., 2007). This is a very important finding as lubrication does not always prevent wear. For example, a graphite pencil provides lubrication but does not prevent wear, enabling a pencil to leave a residue (writing).
Lubricin lubricates via the boundary mode which is a regime in the leftward area of the Stribek curve (Márton and Lantos, 2006). This means that boundary lubrication functions independently of synovial fluid viscosity. These are seminal observations first made by Charles McCutchen a number of years ago who digested synovial fluid with hyaluronidase which eliminated viscosity. This modified synovial fluid continued to lubricate. By contrast, digestion of synovial fluid with trypsin results in a synovial fluid which remains viscous but fails to lubricate.
Ongoing Application
The important role that this mucinous glycoprotein plays is now being studied in a new animal model. Rat joints traumatized in vivo via a surgically induced ACL injury have been studied using whole joint friction ex vivo (Crisco, et al., 2007) and immunohistochemistry of articular cartilage. The same techniques used to study lubricin murine joints. The ACL injury results in a permanent decrease in lubricating ability and early damage to articular cartilage. This is in contrast to a transient synovitis induced by injected adjuvant (Elsaid, et al. 2007).
The translantional relevance of these findings to acute orthopedic problems have been confirmed in humans. Lubricin levels are indeed low in synovial fluid aspirated from patients who are within a 60-day peri-injury period and remain low up to a year post injury (ORS abstract from 2008). This work is ongoing to identify ways to supplement lubricin levels in traumatized joints.
Research Support
Lubricin In Articulating Joints. National Institutes of Health. National Institute of Arthritis, Musculoskeletal and Skin Diseases, RO1 AR050180-01. Jay, GD. Co-Investigator with Matthew Warman MD at Case Western Reserve University. $2,159,560 awarded 7/1/03 - 8/31/08.
Acquisition of a Nanoindentation System for Multi-disciplinary Research and Education in Nano and Bio-mechanics of Materials. National Science Foundation CMS-0421199. Jay, GD. Co-Principal Investigator with P.R. Guduru, B.W. Sheldon, R.F. Cooper and K-S. Kim. $249,515 awarded 7/15/04 - 6/30/05.
Lubricin in ACL Deficient Joints. Centers of Biomedical Research Excellence (COBRE) NCRR, 1P20RR024484-01. Jay, GD. Investigator. $1,147,751 awarded 9/1/07 - 8/31/12. Department of Orthopaedics at Brown Medical School. Qian Chen (Program Project PI).